rsc cp c3cp50620g 3. · chemistry to advanced applications this perspective article summarizes...

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A perspective article from Muruganathan

Ramanathan, Lok Kumar Shrestha, Taizo Mori,

Qingmin Ji, Jonathan P. Hill and Katsuhiko Ariga

Title: Amphiphile nanoarchitectonics: from basic physical

chemistry to advanced applications

This perspective article summarizes research on the self-assembly

of amphiphilic molecules such as lipids, surfactants or block

copolymers that are a focus of interest for many colloid, polymer,

and materials scientists and which have become increasingly

important in emerging nanotechnology and practical applications.

Solution systems are introduced before progression to interfacial

systems, which are roughly categorized as (i) basic properties of

amphiphiles, (ii) self-assembly of amphiphiles in bulk phases,

(iii) assembly on static surfaces, (iv) assembly at dynamic interfaces,

and (v) advanced topics from simulation to application.

As featured in:

See Katsuhiko Ariga et al.,

Phys. Chem. Chem. Phys.,

2013, 15, 10580.

10580 Phys. Chem. Chem. Phys., 2013, 15, 10580--10611 This journal is c the Owner Societies 2013

Cite this: Phys. Chem.Chem.Phys.,2013,15, 10580

Amphiphile nanoarchitectonics: from basic physicalchemistry to advanced applications

Muruganathan Ramanathan,*a Lok Kumar Shrestha,*b Taizo Mori,bc Qingmin Ji,b

Jonathan P. Hillbc and Katsuhiko Ariga*bc

Amphiphiles, either synthetic or natural, are structurally simple molecules with the unprecedented

capacity to self-assemble into complex, hierarchical geometries in nanospace. Effective self-assembly

processes of amphiphiles are often used to mimic biological systems, such as assembly of lipids and

proteins, which has paved a way for bottom-up nanotechnology with bio-like advanced functions.

Recent developments in nanostructure formation combine simple processes of assembly with the more

advanced concept of nanoarchitectonics. In this perspective, we summarize research on self-assembly of

amphiphilic molecules such as lipids, surfactants or block copolymers that are a focus of interest for

many colloid, polymer, and materials scientists and which have become increasingly important in

emerging nanotechnology and practical applications, latter of which are often accomplished by

amphiphile-like polymers. Because the fundamental science of amphiphiles was initially developed for

their solution assembly then transferred to assemblies on surfaces as a development of

nanotechnological techniques, this perspective attempts to mirror this development by introducing

solution systems and progressing to interfacial systems, which are roughly categorized as (i) basic

properties of amphiphiles, (ii) self-assembly of amphiphiles in bulk phases, (iii) assembly on static

surfaces, (iv) assembly at dynamic interfaces, and (v) advanced topics from simulation to application.

This progression also represents the evolution of amphiphile science and technology from simple

assemblies to advanced assemblies to nanoarchitectonics.

1. Introduction

Various functional structures have been created based onso-called nanotechnology.1,2 Most examples rely on sophisticatedfabrication using top-down approaches for preparation of nano-systems from macroscopic objects.3–5 Undoubtedly, top-down nano-technology has an apparent fundamental limitation involving theminimum possible structural dimensions imposed by lithographictechniques. In an alternative approach, bottom-up sponta-neous self-assembly and/or self-organization has recentlyattracted considerable attention.6–11 Excellent examples ofself-assembly processes can be found in biological systems

where highly evolved assemblies of various component mole-cules achieve high functions based on integrated actions.Therefore, materials research based on self-assembly oftenemploys biological molecules such as proteins, nucleic acids,saccharides, and lipids.12–18 Of these, lipids have the simpleststructures and have been widely investigated but their properties(especially their self-assembly properties) can also be extended toanalogous molecules known as amphiphiles. It might be said thatthe study of the self-assembly of amphiphiles is a forerunner tothe development of bottom-up nanotechnology involvingadvanced functions analogous to biochemical systems.

The study of the self-assembly of amphiphilic molecules suchas lipids, surfactants or block copolymers has been a center ofinterest for colloid, polymer, and materials scientists for severalyears and continues to attract attention due to its fundamentalimportance for day-to-day applications in diverse fields includingpharmaceutical, food and cosmetic formulations, catalysis andcontrolled synthesis of nanostructured materials.19–22 The wordamphiphile was introduced by Hartley in 193623 being derivedfrom the Greek amphi meaning ‘both’, and phile, meaning ‘like’(as in prefer) so that the term ‘amphiphile’ denotes a type of

a Center for Nanophase Materials Sciences (CNMS), Oak Ridge National Laboratory,

Oak Ridge, Tennessee 37831, USA. E-mail: [email protected],

[email protected]; Fax: +1-865-574-1753; Tel: +1-865-574-4626b World Premier International (WPI) Research Center for Materials

Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS),

1-1 Namiki, Tsukuba 305-0044, Japan. E-mail: [email protected],

[email protected]; Fax: +81-29-860-4832; Tel: +81-29-860-4597c Japan Science and Technology Agency (JST), CREST, 1-1 Namiki,

Tsukuba 305-0044, Japan

Received 11th February 2013

DOI: 10.1039/c3cp50620g

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PERSPECTIVE

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View Article OnlineView Journal | View Issue

http://dx.doi.org/10.1039/C3CP50620G

http://pubs.rsc.org/en/journals/journal/CP

http://pubs.rsc.org/en/journals/journal/CP?issueid=CP015026

This journal is c the Owner Societies 2013 Phys. Chem. Chem. Phys., 2013, 15, 10580--10611 10581

molecule consisting of two or more different moieties thatinteract differently with, for instance, a particular solvent basedon its polarity.

Sustained interest in amphiphilic systems is due to theirwide range of real life applications. For instance, oil recovery,surfactant enhanced carbon regeneration for waste water treat-ment, herbicide dispersions, de-inking of paper and plasticfilm, filtration of ultrafine particles, stabilization of particulate

suspensions, and as cleaning detergents, etc. In addition tothese known industrial applications, there are also numerousexploratory usages of amphiphiles in modern high technologyindustries. From a fundamental viewpoint, this field remainsan important source of inspiration for researchers from manydifferent scientific disciplines.

In this review a fundamental description of amphiphileassembly is presented and is followed by an application-oriented

Muruganathan Ramanathan

Muruganathan ‘‘Nathan’’Ramanathan is a materialsscientist at the Center forNanophase Materials Sciences atOak Ridge National Laboratory,USA. He received his PhD degreeat the Max-Planck Institute ofColloids and Interfaces, Potsdam,Germany in physical chemistryand materials science. Prior tohis current position, he was apostdoctoral fellow at FloridaState University and ArgonneNational Laboratory, USA.

Lok Kumar Shrestha

Lok Kumar Shrestha received hisPhD degree from YokohamaNational University, Japan in2008. He is currently a MANAscientist at World PremierInternational (WPI) ResearchCenter for Materials Nanoarchi-tectonics (MANA) at the NationalInstitute for Materials Science(NIMS).

Taizo Mori

Taizo Mori received his PhD fromthe Department of PolymerChemistry at Kyoto University in2009. He is currently apostdoctoral researcher in theSupermolecules Group at theNational Institute for MaterialsScience (NIMS).

Qingmin Ji

Qingmin Ji earned her PhD (2005)in chemistry from the Universityof Tsukuba. She started workingas a post-doctoral fellow inNational Institute for MaterialsScience (NIMS) from 2006 andbecame a MANA scientist atWorld Premier International(WPI) Research Center forMaterials Nanoarchitectonics(MANA).

Jonathan P. Hill

Jonathan P. Hill received his PhDdegree from Brunel University,UK in 1995. He is currently asub-group leader of the Super-molecules Group at the NationalInstitute for Materials Science.His current research interestsinclude synthesis and propertiesof tetrapyrroles and their supra-molecular manifolds as well asunusual methods for preparingorganic nanomaterials.

Katsuhiko Ariga

Katsuhiko Ariga received his PhDdegree from Tokyo Institute ofTechnology. He is currently theDirector of the SupermoleculesGroup and the PrincipalInvestigator of World PremierInternational (WPI) ResearchCenter for Materials Nanoarchi-tectonics (MANA), the NationalInstitute for Materials Science(NIMS).

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description of advanced amphiphile assembly structures. Becausesurfactants play important roles in amphiphile science andtechnology, those on surfactants would be mainly described.However, amphiphilic molecules with non-rational-surfactantsare involved. Since amphiphile sciences were initially developedas a result of their solution assembly properties and were thentransferred to assemblies on surfaces as a development of nano-technological techniques, this perspective similarly initiallyaddresses solution systems leading to interfacial systems. Recentdevelopments in nanostructure formation combine simpleassembly processes with the more advanced concept of nano-architectonics.24–32 Similarly, amphiphile assemblies have beendeveloped from more traditional assembly structures, such asmicelles, to well designed nanoarchitectures. The organizationof this perspective also attempts to represent the evolution ofamphiphile assemblies into nanoarchitectonics.

2. Basic properties of amphiphiles

Prior to an advanced description of amphiphile assembly,we will briefly introduce basic properties of amphiphiles. Interms of solvophilicity/solvophobicity, an amphiphilic mole-cule contains both hydrophilic (water-loving) and hydrophobic(water-hating) moieties. The hydrophobic portion is usuallyinsoluble in water but is soluble in organic solvents or oils so thatit is often referred to as being lipophilic. It is often a hydrocarbon ora fluorocarbon chain such as an n-alkyl or a perfluoroalkyl group. Ingeneral, the hydrophilic moiety is referred to as the ‘headgroup’ andthe hydrophobic moiety is known as the ‘tail’. The term amphiphileand surfactant are very often used interchangeably. However, in thispaper, we will use preferentially amphiphile because this term coversa wider range of molecules and materials.

2.1. Types of amphiphile

2.1.1. Conventional amphiphiles. Amphiphiles play a varietyof roles in personal care and household detergency includingcleansing, foam formation, conditioning, viscosity controlwhich is combined with safety and mildness in use. The presenceof water-soluble groups such as sulphate or ammonium confers onthem solubility in polar solvents (see Fig. 1). These polar groupsmay be charged (ionic) or neutral (non-ionic) and ionic amphi-philes can be further classified into anionic (negatively charged),cationic (positively charged) or zwitterionic (amphiphiles withboth positive and negative charges). Although amphiphilesusually consist of one hydrophilic polar head group, recentlydimeric amphiphiles containing two hydrophobic tails and twopolar head groups linked together with a short spacer havedrawn considerable interest from industrial and academicresearchers. This relatively new type of amphiphile known asGemini amphiphiles offers several interesting physicochemicalproperties, such as propensity for lowering surface tension andvery low critical micelle concentrations.

2.1.2. Advanced amphiphiles. Amphiphilicity was formerlybased upon a portion of a molecule’s structure being soluble inwater. However, this definition cannot now be consideredgeneral since amphiphilicity can be extended to various media

including organic solvents.33,34 That is, even some compoundsbearing both fluorocarbon and hydrocarbon chains can formbilayer-like assemblies in an appropriate hydrocarbon solvent. Thefluorocarbon group has a low affinity for the hydrocarbon solventand so is solvophobic while, in contrast, hydrocarbon regions aresolvophilic. These two terms, solvophilic and solvophobic, are oftenused instead of hydrophilic and hydrophobic when non-aqueoussolvents are used as surrounding media. If there is an appropriatestructural balance between the solvophilic and solvophobic partsthen assembly structures similar to those involving hydrophobic–hydrophilic amphiphiles can be formed.

Another extension of amphiphilicity obviates the necessityof intrinsically amphiphilic molecules in the formation ofamphiphile assemblies. Requirements of amphiphilicity canbe satisfied by different types of molecules in admixture (e.g. onesolvophilic and one solvophobic) that can form amphiphilic unitsthrough some specific supramolecular interactions. For example,when a cyanuric acid derivative containing a hydrophilic regionis mixed with a melamine derivative containing hydrophobictails assemblies similar to lipid bilayers are formed throughcomplementary hydrogen bonding.35,36

Amphiphilic assemblies are not limited to purely organicstructures. Sophisticated amphiphile design allows us to prepareorganic–inorganic hybrid assemblies. For example, amphiphileswith alkoxysilane heads have been used to form hybrid assem-blies.37–42 At the surface of these assemblies, cross-linked silanolgroups form an inorganic silica-like structure. This structure iscalled a cerasome because it has both a ceramic-like surface anda liposome-like cell structure. The cerasome is mechanicallystable and can be further assembled into a multi-cellular formwithout causing the vesicular structure to collapse. Inorganicmaterials such as nanoparticles and nanocrystals can also beused for amphiphilic assemblies and are described in a latersection of this paper.

Fig. 1 Typical examples of conventional amphiphiles.

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2.2. Surface activity

Surfactants are major members of amphiphile families. A keycharacteristic of surfactants is their ability to lower the surfacetension at an air–water interface. The word surfactant originatesfrom its use to describe surface-active agents which can adsorbat surfaces or interfaces and markedly alter the surface orinterfacial free energy. The term ‘interface’ indicates a boundarybetween any two immiscible phases while the term ‘surface’denotes an interface where one phase is usually a gas or air.Amphiphilic molecules tend to adsorb at an air–water interfaceand consequently reduce the surface tension of water.43 There-fore, amphiphiles are an important class of materials withunique structural features that confer great utility in industrialand biological applications.

Amphiphiles are usually characterized by their tendency toadsorb at surfaces or interfaces; the better the amphiphile, thestronger is the adsorption capacity. When amphiphilic mole-cules are added to water their hydrophobic groups distort thewater structure thus decreasing the entropy of the system withthe result that some of the molecules are expelled from the bulkof the solvent being then adsorbed at the interface (i.e. an air–water interface). In that case, hydrophilic headgroups remainin solution while the hydrophobic tail avoids direct contactwith water. This is because the adsorbed molecules at theinterface have to be arranged with hydrophilic portions incontact with the water phase and hydrophobic portions orientedto the air phase. This orientation at the interface is an importantfactor in determining the change in properties of the interfaceinduced by the presence of the amphiphile. The properties of aninterface having adsorbed molecules may vary greatly dependingon the orientation of these molecules.

3. Self-assembly of amphiphiles in bulkphases

Assembly behaviours in bulk solution phases have been intensivelyinvestigated including well known assemblies such as micelles,liposomes, and vesicles.44–51 Although developments in nano-scale observations such as scanning tunneling microscopy (STM)and atomic force microscopy (AFM) provide many opportunities fordetailed investigation of amphiphile assemblies on surfaces, amphi-phile assemblies in bulk solution have maintained their crucialimportance in science and technology. These assemblies havegreat possibilities for practical usage in various applications. Inthis section, examples of amphiphile assemblies are introduced.

3.1. Micelles and critical micelle concentration (CMC)

The amphiphilic nature of some molecules leads to their self-aggregation into a variety of structures in aqueous and nonaqueoussolvent systems. Micelles are important structures formed bythe association of all types of amphiphiles in solution. Micellesconsist of inner hydrophobic cores shielded from water by asurrounding corona formed by the hydrophilic headgroupsof the amphiphile. Micelle formation is a spontaneous self-assembly process above a certain concentration of amphiphile

called the critical micelle concentration (CMC) (Fig. 2A).52–62

Several physicochemical properties change abruptly at CMC asshown in Fig. 2B. Assemblies of amphiphiles can have variousmorphologies including spheroid, ellipsoidal prolate, short-to-long rods, flexible rods or wormlike micelles, disk-like structure,or branched chain forms, resulting in various phases such ascubic, hexagonal, lamellar, and cage (Fig. 3). This depends onthe packing of amphiphilic molecules within the aggregatestructure. This will be discussed later.

The thermodynamic properties of amphiphiles in solutionare influenced by the strong tendency of hydrophobic tails toavoid direct contact with water, which is often termed as thehydrophobic effect and leads to the association of amphiphilicmolecules into micelles.63,64 Micellization (the micelle formationprocess) is also expected as the result of an entropy effect.65,66 Theenthalpic contribution results partly from the energetically favorableoptimization of interactions between the hydrophobic tails ofamphiphiles whereas the entropic contribution arises from thelocal structure of water due to hydrogen bonding. Segregatedamphiphilic hydrocarbon chains interrupt hydrogen bondingbetween water molecules causing locally a more ordered

Fig. 2 Changes in physical properties at critical micelle concentration (CMC): (A)surface tension; (B) various other parameters.

Fig. 3 A few examples of surfactant self-assembled structures of amphiphilicmolecules in the bulk phase.

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structure, which is entropically unfavorable. Micelles are formed toavoid disruption of the water structure. These aggregated structuresare entropically more favorable than the segregated amphiphilicmolecules. Micellization can also be considered as an alternativemechanism to adsorption at the interfaces for removing hydro-phobic groups from direct contact with water, thereby reducingthe free energy of the system. Micelles are thermodynamicallystable species that are in equilibrium with the free ‘monomers’(unassociated amphiphilic molecules). It should be noted that theamphiphilic molecules behave very differently when present as freemonomers in solution than in micelles. It is only the free monomersthat contribute to reductions in surface and interfacial tensions andvariations in dynamic properties, such as wetting and foaming. Themicelles serve as reservoirs for amphiphilic monomers.

3.2. Solubilization in micelles

Micelles are important in a number of industrial and biologicalprocesses due to their potential ability to solubilize organic mole-cules. Compounds such as oils, drugs or dye molecules or flavorcompounds that are practically insoluble in water can be solubilizedin the hydrophobic (oily) core of the micelles.67–71 This is very usefulin pharmaceutical formulations where water-insoluble drug com-pounds need to be delivered, and similarly in the incorporation offragrance and coloring agents into cosmetic products. Micelles arealso important in detergency. Dirt or oily stains can be removed byapplying a micellar solution to affected areas. Solubilization capacityof the micellar solution is generally expressed as the ratio of theconcentration of the solubilized molecules to the concentration ofamphiphile in micellar solution. This ratio is usually not very largealthough it can be varied depending on the system components.Further addition of oils above the solubilization limit may result inturbid solutions, which on stirring yield an emulsion. Addition ofco-amphiphile (e.g. a medium chain length alcohol) to such anemulsion often results in transparent or translucent systems referredto as microemulsions. Microemulsions are macroscopically homo-geneous mixtures of oils, water and an amphiphile, which on themicroscopic level consist of individual domains of oil and waterseparated by a monolayer of amphiphile.72–75 They are thermo-dynamically stable.

At higher amphiphile concentrations above CMC, amphiphilicmolecules self-assemble into lyotropic liquid crystalline phases.76–84

Lyotropic liquid crystals lack full three-dimensional translationalorder of molecules of their crystal lattices. Typical lyotropicliquid crystalline phases are bilayer structures of amphiphilesseparated by solvent often called lamellar phases, a two dimen-sional structure formed by the hexagonal packing of rodlikemicelles known as a hexagonal phase and a three dimensionalstructure formed by the packing of spherical micelles known asa cubic phase. The geometry of the self-assembled structurescan be determined by the packing of amphiphilic moleculesand also in terms of interfacial curvature.

3.3. Interfacial curvature, critical packing, and geometry ofaggregates

Self-assembly behaviour of amphiphiles at higher concentra-tions above CMC can be described using appropriate models.85

The first is based on the curvature of an amphiphilic film at aninterface while the second model is based on the moleculararchitecture of the amphiphilic molecule itself (Fig. 4).

The first model involving the interfacial curvature of acontinuous amphiphilic film is based on calculations of thedifferent geometries of surfaces. A surface can be described bytwo main types of curvatures: mean and Gaussian. The principlecurvatures, c1 and c2, define both the mean (H = (c1 + c2)/2) andthe Gaussian (K = c1c2) curvatures. The hydrophilic headgroupon the side of the water interface and the hydrophobic tail onthe other side of the interface determine an optimal curvaturealso known as a spontaneous curvature, which in turn deter-mines the geometry of the aggregates. Aggregates enclosingpolar head groups and water (reverse micelles) are regarded tohave negative curvatures; on the other hand, aggregates withinteriors filled with lipophilic chains (normal micelles) havepositive curvatures.

The second model, i.e. critical packing parameter (cpp) isbased on the packing of amphiphilic molecules. The effectivearea of the hydrophilic headgroup of surfactants, a, with respectto the length of the hydrophobic tail, lc, for a given molecular

Fig. 4 Molecular structure of amphiphilic molecules, preferred aggregate struc-tures, and the related aggregate curvature.

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volume, v, controls the interfacial curvature. The effective areaof an amphiphile’s headgroup or an effective molecular cross-sectional area is due to the balance between the hydrophobiceffects for assembly of the amphiphile tails (which causes theorganization of amphiphilic molecules and, hence, reduces a)and the tendency of hydrophilic headgroups to maximize theircontact with water (and increases a). The balance between thesetwo opposing forces leads to an optimal area per amphiphilicheadgroup, as, for which the interaction energy is minimum.

In order to determine the micellar shape a dimensionlessparameter, cpp, is introduced, which is defined as v/aslc, wherev and lc are the volume and extended length of the hydrophobicalkyl chain and as is the area occupied by an amphiphilicmolecule at the micelle–water interface. As mentioned earlier,as is determined by the cross-sectional area of the amphiphilicheadgroup and the various interactions during micelle formation.On the other hand, the extended length of the alkyl chains for asaturated hydrocarbon with n carbon atoms, lmax, and volume vcan be estimated by Tanford’s equation.

lc r lmax E 0.154 + 0.1265n nm (1)

v E (27.4 + 26.9n) � 10�3 nm3 (2)

The extended length lc is approximately 80% of the lmax value.After the cpp of an amphiphilic molecule has been estimatedfrom its molecular dimensions, a rough idea of the shape of theaggregates can be given.

3.4. Normal micelles in the aqueous system

We know that the intrinsic geometry of an individual amphi-philic molecule has a strong influence on the morphology of itsmicelles and that the shape of the micelles can be determinedby the cpp. The cpp values for spherical, cylindrical, and lamellarparticles are B1/3, 1/3 o cpp o 1/2, and 1/2 o cpp o 1,respectively. Previous investigations have revealed formation ofspherical micelles just above the CMC. However, this spheroidgeometry of micelles can be modulated into other geometriessuch as prolate, rods or disks or ordered liquid crystalline phasesby variation of control parameters such as concentration,temperature, salinity, and pH.

Here we discuss the general effect of volume fraction ofamphiphile on the micellar structure. As mentioned earlier,micelles are formed at CMC due to the hydrophobic interaction,and the shape of the micellar aggregates varies depending on thevalue of cpp. Upon further increases in amphiphile concentrationabove CMC repulsive intermicellar forces emerge and operatenormal to the interface. Repulsive intermicellar interactions suchas electrostatic repulsion induce micelle ordering at a certainamphiphile volume fraction and with symmetry that dependson the micellar shape. For instance, spherical micelles closepack into a cubic array forming the discontinuous cubic phase.Similarly, rodlike and lamellar micelles pack into hexagonaland lamellar phases respectively. By this simple approach, foran amphiphile forming spherical micelles (cpp o 1/3) thephase sequence, from spherical micelles to the cubic phase tothe hexagonal phase to the lamellar phase, can be expected

depending on the amphiphile concentration. If the amphiphileforms elongated micelles (1/3 o cpp o 1/2) then the phasefollows a sequence of elongated micelles to the hexagonalphase to the lamellar phase.

As mentioned previously, intermicellar interactions operatenormal to the micelle–water interface so that any decrease inthe intermicellar distance with rising amphiphile concen-tration increases the free energy of the system. Another possibleroute for the system to compensate this excess free energycaused by an increase in amphiphile concentration is throughmicrostructure transformation, i.e. a transition from spherical-to-cylindrical micelles or from cylinder-to-planar micelles.

3.5. Reverse micelles in the nonaqueous system

In recent years, there has been increasing interest in studyingthe self-assembly behaviour of amphiphiles in nonpolar solventswith a small amount of water because of the wide range ofpotential applications.86,87 Generally, lipophilic amphiphilesform reverse micelles in nonpolar solvents. Reverse micelleshave structures in contrast to those of conventional micelles inwater. Reverse micelles consist of a polar headgroup orientedtoward each other at the interior of a micelle with the hydro-phobic groups oriented towards the exterior hydrophobicenvironment of a nonpolar solvent.88–92 That is, reversemicelles have a watery core with nonpolar lipophilic chains ofthe amphiphile as a shell. Likewise in a normal micelle system,reverse micelles can have various shapes and sizes dependingon both the amphiphile and solvent.

It should be noted that the solution behaviour of amphiphilicmolecules in nonaqueous mixtures differs markedly from thatin aqueous systems. It is well known that when amphiphileconcentration increases physical, colligative, and spectralproperties of the aqueous system undergo an abrupt changeover a narrow region of concentration (at CMC). However, thephysical properties of amphiphile solutions in nonaqueousmedia change gradually with amphiphile concentration, i.e.there is not any sharp transition in the solution properties withincreases in amphiphile concentration.93 This is why the existenceof CMC in nonaqueous systems has been questioned. However,previous experiments have shown evidence of the formation ofaggregate structures (reverse micelles) in nonaqueous systemseven at low amphiphile concentrations.

In contrast to aqueous systems, the structure of solventremains largely unaffected by the addition of amphiphiles tononaqueous media. The hydrophobic tail of a single dispersedamphiphile interacts only with the solvent, whereas if incorporatedinto an aggregate (reverse micelle) it interacts with both thesolvent and neighboring hydrophobic groups within the sameaggregate. However, the dispersion forces between organicmolecules depend only on the intermolecular distance so thatdispersion interactions of a hydrocarbon tail in an aggregate andthose of a hydrocarbon tail in a single dispersed amphiphile arepractically the same. Headgroups of ionic amphiphiles remainlargely in an un-dissociated state in nonaqueous organicsolvents and behave essentially as dipoles, and the headgroupsof nonionic amphiphiles also possess a permanent dipole moment.

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When the amphiphiles are singly dispersed, the headgroup inter-acts with solvent through dispersion forces, dipole induced-dipoleinteractions, and, in aromatic solvents, through charge-transferinteractions. These interactions are also negligible.

The polar headgroups of amphiphiles within the aggregatesinteract via dipole–dipole, dipole-induced dipole, dispersion,and closed shell repulsion interactions of which the dipole–dipole interaction is the most important. In systems whereintermolecular hydrogen bonds or metal coordination bondsexist between amphiphilic headgroups, these bonds makesignificant contributions to reverse micelle formation inaddition to those due to the interactions between the polarheadgroups.94 Furthermore, the transfer of free energy ofhydrophilic headgroups from a hydrophilic environment toan oily hydrophobic environment may provide insight intothe mechanism of reverse micellar formation.

Concentration dependence of aggregation number, Nagg,gives an idea of the micellization process and also of thedistribution of micellar size in nonaqueous media. The Nagg

of several ionic amphiphiles is negatively affected by theconcentration of the amphiphiles. For instance, nonaqueoussolutions of barium or calcium dinonylnaphthalene sulfonates,sodium 1,2,-bis(2-ethylhexyloxycarbonyl)ethane sulphonate oraerosol OT (sodium 1,2-bis(2-ethylhexyloxycarbonyl)-l-ethane-sulfonate, AOT) are characterized by a constancy of amphiphilicmonomers over a wide range of concentration and by a narrowdistribution of the micellar size.95–97 However, the aggregationnumber of nonionic amphiphiles in nonaqueous systemsincreases either linearly or according to the Langmuir adsorp-tion isotherms with the amphiphile concentration.

The nature of the solvent is one of the factors affectingthe micellar size in nonaqueous systems.98,99 The solventdependence of Nagg has been studied for a variety of anionicand cationic amphiphiles in nonaqueous systems. However,the solvent dependency of Nagg of the nonionic amphiphiles islimited because of their poor solubility in these media. Thestudy of temperature dependence of CMC or the aggregationnumber in nonaqueous systems is very important from athermodynamic point of view. With the few data available onsuch studies of nonionic amphiphiles, it has been shown thatthe aggregation number decreases with increasing temperaturealthough this is not consistent with some dependency onthe solvents present. For example, the aggregation numberof sorbitan monolaurate micelles increases with increasingtemperature in benzene.100

Compared to normal micelles in aqueous systems, thestructure (shape, size and internal cross-sectional structure)control of reverse micelles in nonaqueous systems is not asimple matter because of their inverted structures and lesserfreedom in variation of the control parameters. However, recentdevelopments in the free structure control of reverse micelleshave shown that micellar growth can be achieved by replacingwater with other molecules such as formamide, glycerol orurea, and also upon addition of amphiphilic salts.101–106 Theionic amphiphile AOT and lecithin phospholipid are the mostcommon amphiphiles used for the study of reverse micelles.

These amphiphiles form reverse micelles or water in oil (W/O)microemulsions in amphiphile–oil–water ternary mixtures.107–116

The structure of such micelles has been found to depend on theextent of water solubilization in the micellar core. Recentstudies of nonionic amphiphilic reverse micelles have shownthat glycerol- or sugar-based nonionic amphiphiles potentiallyform reverse micelles in a variety of organic solvents in theabsence of water.117–123

Formation of uncharged reverse wormlike micelles hasrecently been realized in sucrose-based nonionic amphiphile–oil systems in the absence of water under ambient conditions.This route involves the addition of sucrose dioleate (SDO) tosemi-dilute solutions of sucrose trioleate (STO) in hexadecane.It should be noted that it had only been possible to form reversewormlike micelles using ionic amphiphiles (AOT or phospho-lipid lecithin) where water and/or salts are essential to inducemicellar growth. However, it has been shown that a lesslipophilic nonionic amphiphile SDO promotes one-dimensionalgrowth of STO reverse micelles and leads to the formation oftransient networks of viscoelastic reverse wormlike micelles. Thezero-shear viscosity increases by B4 orders of magnitude andthe mixing fraction of SDO to STO determines the growth. Inamphiphile self-assembly, the co-presence of polar and nonpolarsolvent and ‘strong’ amphiphile bearing charge are common.Thus, the unusual case of the SDO–STO system could be interestingfrom the viewpoint of practical applications since the presenceof both charge and water can be avoided.

3.6. Vesicles in aqueous systems: normal vesicles

Vesicles are closed shells of amphiphile or lipid bilayers whichform in a solvent and have typical sizes of 10–100 nm124 but canalso reach dimensions in the range of several hundreds ofnanometers to several micrometers. They are hollow aggregateswith a shell composed of single or multiple amphiphile or lipidbilayers. Vesicles formed in aqueous systems are called normalvesicles in which membranes are separated by a water phasewith the hydrophilic part of the amphiphile oriented to theexterior of the membrane as shown in Fig. 5. A vesicle formedfrom a single bilayer structure is called a unilamellar vesicle(Fig. 5A), whereas those formed from multiple bilayers areknown as multilayer vesicles (Fig. 5B). Normal unilayer orunilamellar vesicles have a classical structure where a normalbilayer, composed of two monolayers with their hydrophobicparts facing each other, forms a closed shell in aqueous solvent.Vesicles formed by lipids are known as liposomes. Vesicles orliposomes are important model systems for biological membranesand for fluid surfaces. They have drawn considerable attention invarious fields including drug delivery, pharmaceutical formula-tions, cosmetics, and also in materials architectonics.125–131 Vesicleformation and fusion are anticipated to be important in manyphysiological processes such as cell division and fusion. Indrug delivery or cosmetic applications, vesicles act as deliveryagents for encapsulated materials. For targeted drug deliveryapplications, vesicles are formulated from amphiphilic orphospholipid molecules in the presence of the drug moleculesto be encapsulated then the vesicle solutions are injected into

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the bloodstream where vesicles can carry the drug protecting itfrom unwanted release. Since vesicles can potentially bind tocell membranes, they are effective in delivering the drugdirectly to cells.

Cholesterol is an important constituent of liposomes as itplays a crucial role in stabilizing the bilayer structure ofliposomes. Cholesterol orients itself within the space adjacentto phospholipids due to its relatively small size. However, itshould be noted that cholesterol cannot itself initiate theformation of a bilayer structure. Cholesterol also preventstilting and distortion of the membrane structure at tempera-tures exceeding the phase-transition temperatures. Dependingon the hydrophilic headgroup of the amphiphile, liposomesmay be charged or neutral (uncharged). For charged liposomes,stability is largely determined by the magnitude and the rangeof electrostatic interactions. For zwitterionic phospholipidswith a zero net charge, liposomes repel each other and conse-quently possess colloidal stability. Similar to phospholipids,nonionic amphiphiles may also self-assemble into a closedbilayer structure. This generally requires external energy in theform of physical agitation or heat. Some nonionic amphiphiles(glycerol-based) may spontaneously form vesicles in water.

Vesicles are usually thermodynamically nonequilibriumsystems which can however be kinetically stable over quite longperiods of time. There are several methods for preparation ofvesicles which influence the shape, size, polydispersity and typeof vesicle obtained. The classical phospholipid vesicles arenormally prepared by sonication of a lamellar phase dispersionin the two-phase region composed of the lamellar phasein equilibrium with an excess aqueous phase. Lamellae arebroken by ultrasonication and can then reassemble as vesicles.This leads to smaller vesicles with a wide size distribution since

the mechanical action of sonication is inhomogeneous. Theresulting vesicles are considered to be only metastable. Over timethey relax back to a stable two-phase equilibrium. Occasionally,multilayer vesicles form spontaneously upon dissolution andgentle agitation of phospholipids in water. Dissolution of alamellar phase formed at higher concentrations into excesswater also produces vesicles. Another method involves thedispersion of amphiphiles in an organic solvent followed byinjection into an excess of water. Giant unilamellar vesicles areformed by this method as the organic solvent evaporates.Multilamellar vesicles with a narrow size distribution can beprepared by applying a steady shear to the lamellar phase. Inthis case, the mechanical deformation is more uniform incomparison to sonication. The average size of vesicles can becontrolled by varying the applied shear.

In the past, spontaneous vesicle formation has been formulatedin certain mixtures of short- and long-chain, double-tailedlecithins,132 in solutions of double-tailed amphiphiles withhydroxides and other more exotic counterions,133,134 and alsoin some mixtures of single-tailed amphiphiles135 as an improve-ment over conventional vesicles formed by sonication. However,up until the 1980’s the relatively restricted chemical or physicalproperties of the vesicles and systematic methods of vesiclepreparations were not widely exploited. Kaler et al. thenproposed a general method for preparing spontaneous, equili-brium vesicles of controlled size, surface charge, or permeabilityfrom commercial amphiphiles.136 Vesicles formed immediatelyupon combining aqueous mixtures of two commercially avail-able, single-tailed amphiphiles with oppositely charged head-groups. They proposed that this method is a remarkably simpleway of tailoring vesicle properties and allows gentle andefficient encapsulation to take place without mechanical orchemical perturbations from the final vesicle composition orstructure. It should be noted that the curvature of the mixedamphiphile bilayers (which controls size and shape), the vesiclewall thickness (which controls permeability), and the sign andmagnitude of the surface charge (which control vesicle inter-actions and stability against aggregation) can be determined bythe relative amounts and the chain length of the individualamphiphiles used. The vesicles prepared from aqueous mixturesof cetyl trimethylammonium tosylate (CTAT) and sodium dodecyl-benzene sulfonate (SDBS) range from about 30 to 80 nm inradius. And again the size depends on the amphiphile ratio andtotal concentration. Vesicles prepared from these systems arestable for at least 1 year.

3.7. Vesicles in nonaqueous systems: reverse vesicles

Vesicles formed in nonaqueous media are known as reversevesicles and contain membranes separated by the oily phasewith the hydrophobic part of the amphiphile oriented to theoutside of the membrane as shown in Fig. 5C. Reverse vesiclesconsist of bimolecular layers of amphiphiles whose hydrophilicpart is located in the interior of the concentric bilayers and aredispersed in nonaqueous media. Unlike vesicles observed inaqueous systems, reverse vesicles in nonaqueous media arerelatively uncommon although they may find many applications

Fig. 5 Schematic representation of normal (unilamellar (A) and multilamellar(B)) and reverse (multilamellar) vesicles (C).

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such as for the encapsulation and controlled delivery of hydro-philic solutes or in tailored synthesis of nanostructured materials.Kunieda et al. for the first time demonstrated the formation ofreverse vesicles using the nonionic amphiphilic tetraethyleneglycol dodecyl ether.137 This amphiphile dissolved in dodecaneformed isotropic solutions without any liquid crystalline struc-ture in the amphiphile–oil binary mixture. However, uponaddition of a small amount of water, the isotropic solutiondivided into a lamellar liquid crystalline phase, which was inequilibrium in the excess oil phase. The reverse vesicles formedby hand shaking of this two-phase system containing a lamellarliquid crystal and an excess oil phase have wider size distribu-tions with diameters in the range from 10–20 mm and, likenormal vesicles, coalesce and revert to a lamellar phase afterstanding. In the study of phase equilibria in the water–tetra-ethylene glycol dodecyl ether–dodecane system, Kunieda et al.found that lamellar liquid crystal swelling of a large amount ofoil coexists with an excess oil phase in the oil-rich region inwhich reverse vesicles form.138 The inside and the outside ofthe reverse vesicles are oil. The shapes of the reverse vesiclesare dependent on the oil content in lamellar liquid crystals.They also found stable reverse vesicles (with stability greaterthan 6 months) in a water–sucrose monoalkanoate–hexanol–decane system although the size distribution was very large inthe range of 100 nm to 5 mm.139 They found that the interlayerspacing of bilayers increased upon addition of hexanol and thushexanol is regarded as being effective in making the bilayersflexible and in dispersing the liquid crystal as reverse vesicles.

The Kunieda group also demonstrated for the first timereverse vesicles containing ionic amphiphiles and concludedthat a combination of less hydrophilic oil-soluble ionic amphiphileand hydrophilic amphiphile is important for the formulation ofreverse vesicles.140 Moreover, addition of a small amount ofwater is also crucial to adjust the interactions of the hydrophilicpart of reverse vesicles. In the presence of a small amount ofwater, a lamellar liquid crystal containing a large amount of oilis formed in the AOT and sodium dodecyl sulfate (SDS) system.When the liquid crystal is dispersed in oil, reverse vesiclesare formed.

Several other groups later also formulated reverse vesiclesbased on sucrose esters,141 amino acid derivatives,142 andmetalloamphiphiles.143 However, questions continue to ariseregarding the stability, robustness, and ease of formulation ofreverse vesicles and the general guidelines for the structurecontrol of such aggregates are unclear. Recently, Tung et al.reported a new route for the formation of stable unilamellarreverse vesicles in the nonpolar organic solvents, cyclohexaneand n-hexane.144 Their method offers a general framework fortuning reverse aggregate geometry from reverse spherical-to-cylindrical micelles and eventually to reverse vesicles using anappropriate combination of long- and short-chain phospho-lipids. The long-chain lipid is L-a-phosphatidylcholine (lecithin),a natural double-tailed lipid with an average tail length of 17carbons and an unsaturation in one of the tails. The short-chainlipid is 1,2-dibutyroyl-sn-glycero-3-phosphocholine (C4-lecithin)with two four-carbon saturated tails. Their method involves

mixing of short- and long-chain lipids (lecithins) in thepresence of a trace amount of sodium chloride. They success-fully controlled the size of reverse vesicle by tuning the ratio ofshort- to long-chain lecithin. Increasing this ratio favored aspontaneous transition from reverse micelles to reverse vesi-cles. Average vesicle size can be tuned from 60 to 300 nmdepending on the sample composition. They suggested thatelectrostatic interactions may be important in reverse vesicleformation and stabilization. Sodium chloride is proposed to actas a glue in binding the lipid headgroups together and instabilizing the vesicles in solution.

4. Assembly on static surfaces

Along with developments in surface analytical techniques asseen in molecular level observation using STM and AFM,amphiphile assemblies at surfaces have attracted much atten-tion. Amphiphile assemblies at surfaces have great potential toconnect molecular phenomena with artificial devices such aselectrodes, sensors and transistors. Various techniques includingself-assembled monolayer (SAM) methods,145,146 Langmuir–Blodgett (LB) techniques,147–156 and layer-by-layer (LbL) assem-blies157–161 have been developed providing well organized anddesigned thin films at interfaces. Although we give briefdescriptions of LB films here, SAM and LbL techniques arenot well described. This section is dedicated to exploratoryresearch on assembly of amphiphiles on static surfaces andtheir applicability as structure directing agents. Anisotropic shapednanoparticles are also ideal building blocks for engineeringand tailoring nanoscale structures for specific technologicalapplications. In this section, the role of amphiphilic assembliesin the controlled growth (synthesis) of inorganic nanomaterialsis discussed in detail.

4.1. Role of amphiphile assemblies in understandingintermolecular forces

The early developments in amphiphilic assembly were centeredaround understanding of static surface forces. Molecular oratomic level short-range forces were first introduced by Langmuirin well-ordered molecular layers of amphiphiles. Developments inquantum mechanics and electromagnetics are key to the formula-tion of theories describing the nature of dispersion forces such asLondon, Keesom, Debye and related long-range surface forces.In combining short and long range forces DLVO (Derjaguin,Landau, Verwey and Overbeek) theory was developed by a teamof Russian and Dutch scientists.162,163 Experimental develop-ments for probing various components of these intermolecularforces commenced soon after the introduction of the surfaceforce apparatus, which is still used today. Current developmentsin this field are primarily exploratory and benefit from thesophistication of modern instruments.

The adsorption of amphiphiles from solutions onto solidsurfaces has been investigated because of the numerous practicalapplications where solid–liquid contact occurs. Both hydrophobicand hydrophilic surfaces carrying charges have been examined. Ithas been postulated that adsorbed amphiphiles will self-assemble

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at the solid–liquid interface in a manner analogous to bulk-phase micellization. The competition between the interactionof the amphiphile-surface and the solvent-surface determinesthe formation of surface aggregates. The most important resultis that the process of surface aggregation takes place at criticalaggregate concentrations (CAC) much lower than the bulkphase CMC. This indicates that the aggregates are truly self-assembled on the surface and that they are not micelles formedin the bulk and subsequently adsorbed on the surface.

It has been postulated that a continuous monolayer ofamphiphile forms on hydrophobic surfaces whereas a continuousbilayer forms on hydrophilic surfaces. However, both anionic (SDS)and cationic (cetyltrimethylammonium bromide, CTAB) amphi-philes are known to form hemicylindrical aggregates on hydro-phobic graphite surfaces where the amphiphile tails are orientedsuch that only the tails are in contact with the surface. Thesehemicylindrical aggregates are transformed into lamellar assem-blies by adding a co-amphiphile (dodecanol) to the system.

According to Brinck, Jonsson and Tiberg, the adsorption ofnon-ionic amphiphiles from their micelle solution to a solid surfaceoccurs in a two-step process where the first step is diffusion fromthe bulk solution to a subsurface, and the second step is transpor-tation from the subsurface to the surface with concomitant adsorp-tion.164 They assumed a finite stagnant layer outside the surfacedue to the convection caused by stirring during measurements(a stirred cuvette geometry). The adsorption was observed to bediffusion controlled, and the concentration immediately outsidethe surface was determined by a local equilibrium in the sub-layerregion as is schematically summarized in Fig. 6.

Very recently, Bain and coworkers have used total internalreflection Raman spectroscopy to look at both the equilibriumand kinetic aspects of adsorption of a cationic amphiphile.165,166

According to them the well-defined wall-jet geometry is sufficient tomodel the mass transport of amphiphile using known hydro-dynamics for the adsorption process. The cuvette and wall-jetgeometries differ in the dimension of the stagnant layer. However,the need for further exploratory research to understand the funda-mentals of amphiphile adsorption on solid substrates is imperative.

As a parallel development to the physiochemical studies onamphiphile assemblies, structure evolution and force measure-ments, synthetic chemists have explored the realm of newamphiphiles with various molecular architectures.167 Adsorp-tion kinetics and microstructures of various gemini (dimeric),zwitterionic amphiphiles have been studied in detail.168 Whileconsiderable attention has been paid to hydrocarbon chain amphi-philes there are only a limited number of reports regarding theadsorption kinetics and microstructures of fluorocarbon tailedamphiphiles or fluoroamphiphiles. In fact, fluoroamphiphiles havebeen used to advantage in a range of applications owing to theirsuperior hydrophobicity, lipophobicity, thermal stability andbioinertness.169 Strong intermolecular interactions betweenfluorocarbon tails are the origin of these unique characteristicsin comparison to their hydrocarbon counterparts.

Fundamental studies of direct adsorption of fluoroamphi-philes on solid surfaces are rare170 in spite of their favorablespreading and wetting characteristics, including low surfacetension, high fluidity, high density and low solubility in aqueousmedia. However, fluoroamphiphile coated surfaces are beingwidely used in biomedical and analytical applications. Forinstance, in bioseparation processes, fluoroamphiphiles are usedas an additive in buffer solutions for (free-flow) capillary electro-phoretic separation of proteins, peptides, and enzymes.171,172

Highly hydrophobic fluroamphiphile coated surfaces are usedfor immobilization of biomolecules, heterogeneous diagnosticassays and in biosensors.173

The adsorbed layer structure of partially fluorinated cationicamphiphiles and their mixtures on mica were determinedusing AFM imaging. It was found that the fluoroamphiphileself-assembled as cylindrical micelles and shape transitions inthe adsorbed layer were correlated with surface and bulkcompositions.174,175 Solvophobic interaction forces are largelystudied in fluorocarbon amphiphilic surfaces but their adsorbedlayer structures are not well understood. Classeon and coworkershave used the nanointerferometric surface force apparatus alsoknown as MASIF (Measurements and Analysis of Surface Inter-actions and Forces) to study the adsorption behaviour andinteraction forces of fluoroamphiphiles adsorbed on solidsurfaces.176,177 Their experimental results indicate that cationicfluoroamphiphiles self-assemble on a variety of solid surfacessuch as silica, glass, and mica in the form of bilayer structures.This adsorption process is influenced by the interaction forcesbetween the adsorbed layers that largely depend on the amphi-phile concentration. At low fluoroamphiphile concentrationthe molecules adsorb both on glass and mica surfaces dueto favorable electrostatic interactions. At higher amphiphileconcentrations hydrophobic interactions continue to drive theadsorption process. Fig. 7 illustrates the structure of twoamphiphile assemblies on the approaching surfaces at variousconcentrations.

4.2. Amphiphilic monolayers on crystalline surfaces forcontrolled nanoscale synthesis and assemblies

Metal and semiconductor nanoparticles and nanocrystals thatexhibit novel and/or enhanced characteristics contingent on

Fig. 6 Schematic illustration of amphiphile equilibrium with layered regions.

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their size and shape are of prime interest in the modern era ofnanotechnology. The current and potential applications ofnanoparticles are growing covering an extremely broad rangeof markets and industries including catalysis, plasmonics,sensing, spectroscopy, biomedicine, renewable energy, cancertreatment, environmental protection, pharmaceuticals, personalcare, surface coatings, textiles, food, plastics, electronics, storagedevices, building materials, automotives, agricultural, etc.178 Inthese applications, control of nanoparticle shape and size iscritical for obtaining required functionality and selectivity. There-fore, the ability to fabricate and control the structure of nano-particles allows scientists and engineers to influence the resultingproperties and, ultimately, design materials to give the desiredproperties. Both top-down and bottom-up processes are used toobtain metal nanoparticles. In the case of bottom-up processes,amphiphilic assemblies play a critical role in developing nano-particles with tunable sizes and different shapes. A syntheticmethod now popularly known as colloidal chemistry has beenwidely used for nanoparticle fabrication.179–181 In this method,surface passivation and self-assembly of amphiphile-coated nano-particles are harmoniously coupled.182

In the process of solution-phase synthesis of metallic, semi-conducting, magnetic, and multicomponent nanoparticlesthe crystalline core is surrounded by a layer of amphiphilicmolecules. These amphiphilic molecules are often referred to asstabilizing agents, capping agents or ligands. Typically, colloidal

nanomaterials are synthesized by reacting appropriate mole-cular precursors, that is, inorganic salts or organometalliccompounds. Nucleation and growth of nanocrystals occurs inthe solution phase in the presence of organic amphiphilicmolecules which dynamically bind to the nanoparticle/nano-crystal surfaces immediately after their nucleation and preventthem from fast growth and coagulation.183–185 In this processamphiphiles play an important role in tuning the kineticsof nucleation and growth for achieving the required shapeand size of nanoparticles. Amphiphiles such as long-chaincarboxylic and phosphonic acids (e.g., oleic acid and n octade-cylphosphonic acid), alkanethiols (e.g., dodecanethiol), alkylphosphines, alkylphosphine oxides (classical examples aretrioctylphosphine, TOP, and trioctylphosphine oxide, TOPO),and alkylamines such as hexadecylamine are commonlyused in the colloidal synthesis of nanoparticles and nano-crystals.186–188 Another significant advantage of having anorganic amphiphilic monolayer as a stabilizing/capping agentis to provide solubility of inorganic nanoparticles in a particularsolvent, which is very important for further processing ofnanoparticles and nanocrystals. Various types of amphiphilesare commonly used as surface ligands with their molecularstructure, interparticle spacing and their function on nano-particle and nanocrystal growth.

Rodlike micelles, microemulsions, reverse micelles andamphiphile assemblies in solutions have been used as a softtemplate to direct the growth of anisotropic nanomaterials.189–192

For instance, Murphy and Jana have demonstrated that theshape of the seed-mediated growth of Au and Ag can beprecisely controlled by a rodlike micellar template made ofCTAB amphiphile assemblies.193,194 In this case moderatelystrong binding of CTAB amphiphiles to the growing crystalphase of Au or Ag helps anisotropic growth of nanorods. Fig. 8illustrates an example of the role of amphiphile assemblies indetermining the shape of the nanoparticles and nanocrystals.The aspect ratios of the resulting nanorods and nanowires arecontrolled by the shape and size of the micellar templates andby the relative concentration of precursors, salts, and amphiphiles.Besides CTAB, micelles derived from SDS or AOT amphiphilesalong with other co-amphiphiles are often used as soft templates.Here, we aim to demonstrate how these amphiphile assembliesdirect the growth of solid surfaces.

Fig. 7 Illustration of the structure of amphiphile assemblies on approachingsurfaces at various concentrations.

Fig. 8 An example of the contribution of amphiphile assemblies to formation ofthe anisotropic shapes of the nanoparticles and nanocrystals.

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In addition to size and shape, precursors and amphiphilescan control the crystalline phase of the nanoparticle. Differentligand coverage on different nanocrystal facets can lead toanisotropic interactions between nanocrystals by changingtheir effective shape. For instance, Choi et al. have shown thatPbS nanocrystals pack into superlattices of different symmetry,depending on their degree of aging in solution, due to selectivedetachment of oleic acid (OA) ligands from the 100 facets of therock salt (RS) core.195,196 Bealing et al. have shown that the changein surface energies with ligand coverage of these two surfaces ispredicted to give rise to equilibrium nanocrystal shapes rangingfrom octahedra to cuboctahedra to cubes, in accordance withexperimentally observed shapes of Pb-salt nanocrystals cappedwith OA� as shown in Fig. 9.197

Mann and coworkers have demonstrated that the interfacialactivity of reverse micelles and microemulsions can beexploited to couple nanoparticle synthesis and self-assemblyover a range of length scales.198,199 It can lead to materials withcomplex organization arising from the interdigitation ofamphiphilic molecules attached to specific nanoparticle crystalfaces. According to their model of adsorption, interdigitationand aggregation, it should be possible to produce 1D nanowiresand higher order colloidal architectures using amphiphileswith headgroups complementary to the crystal surface of thenanoparticles. In a different report, Filankembo and Pileni havedemonstrated that the shape of the nanoparticles can becontrolled without affecting the macroscopic structure of theamphiphile templates by simply adding the Hofmeister seriesof salt ions.200

4.2.1. Controlled assembly of metal nanoparticle–amphi-phile hybrids. So far we have reviewed some of the novelapplication and exploratory research in the field of amphiphilicassembly directed growth of inorganic nanomaterials. Oncegrown, further scientific and technological advances in theapplication of nanorods in functional devices depend on theability to organize them in complex one- or multi-dimensionalfunctional architectures. Also, to enhance their electronic andoptical properties, the anisotropic nanorods need to be organizedin a controllable and predictable fashion. In order to achieve theself-assembly of nanorod arrays surface chemistry of the nanorodsis often modified. For instance, end-to-end or side-to-sidenanorod assemblies can be obtained using chemical or physicalbinding of ligands that stabilize nanoparticles. Here the shape

tunability is limited to the ligand–ligand interactions. Thus, toobtain varying self-assembly structures of nanorods, their sur-face chemistry has to be changed by replacing or modifyingligands. Nie et al. have introduced a new ‘‘block copolymer’’paradigm for the self-assembly of nanorods. In this approach,they have organized metal nanorods in structures with varyinggeometries using a striking analogy between amphiphilic ABAtriblock copolymers and the hydrophilic nanorods tethered tohydrophobic polymer chains at both ends. Here the self-assembled structure is directed by the thermodynamics andkinetics of the system. The tunability and reversibility of theassembly were achieved solely by changing the solvent qualityfor the constituent blocks. Using this amphiphilic materialsassisted assembly process, they have demonstrated a range ofstructures including rings, linear and bundled chains andnanospheres with 2D walls as shown in Fig. 10.201

4.2.2. Advantages, limitations, challenges and opportu-nities. Of the advantages of amphiphile directed colloidalsynthesis, we would like to emphasize the excellent controlover size and shape of prepared nanostructures and theirapplicability to a broad range of materials (metals, semi-conductors, quantum dots etc.). Moreover, the use of relativelysimple experimental equipment and chemicals allows one toobtain high quality materials and tailor their properties atsurprisingly low cost. Using this process significant successhas been achieved in synthesis of nanocrystals and nano-particles of different technology inspired semiconductorsincluding II–VI (CdSe, CdTe, CdS), III–V (InP, InAs) and IV–VI(PbS, PbSe, PbTe) semiconductors. State-of-the-art exploratoryresearch in this field includes synthesis of more complex andsophisticated structures where size, shape, and connectivitycan be independently tailored in multicomponent systems.Development of core–shell structures, dumbbell morphologieswith high level of monodispersity with the size range ofsub-20 nm are all ongoing research endeavors. In spite of

Fig. 9 Effect of ligand coverage on equilibrium nanocrystal shapes ranging fromoctahedra to cuboctahedra to cubes.

Fig. 10 Structures including rings, linear and bundled chains and nanospherescoated with amphiphiles and block copolymers.

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rapid progress having been made in the last few decades theempirical synthetic procedures are still naıve in terms of ourfundamental understanding. For instance, amphiphiles(soft templates) are dynamic in solution and the stability ofthe amphiphile assemblies during crystal growth remainsuncertain.202 Charged amphiphiles such as SDS or CTAB mightform complexes with metal salt precursors ultimately affectingthe reduction kinetics but which is not clearly understood.203 Acommonly accepted but not proven mechanism is that thefunctionality of amphiphile is similar to growth-directingadsorbates on metal surfaces than a physical template for metalreduction. For technological applications, particularly in semi-conductor technology, pure, all-inorganic and highly crystallinematerials are preferred. Therefore, structure directing agents(hydrocarbon amphiphiles) should be removed to facilitatecharge transport in arrays of metallic nanocrystals. Advantagesof using amphiphiles over SAMs (thiols, silanes, amines etc.) asstructure-directing agents are their moderate affinity to thegrowing crystal planes which can be removed relatively easilycompared to hydrocarbons with anchoring end groups. Severalexcellent papers promote the detailed understanding of organicamphiphiles (ligands) in colloidal synthesis of nanoparticlesand nanocrystals and their subsequent removal and exchangefor smaller molecules.204–207

4.3. Assembly and application of superamphiphiles on staticsurfaces

Block copolymers exhibit a wide range of phase-separatedmorphologies in bulk, on surfaces and at interfaces. Diblockcopolymers consisting of both hydrophobic and hydrophilicblocks are naturally amphiphilic and they are often referred toas ‘‘superamphiphiles’’. The self-assembly of these large mole-cular weight amphiphiles depends strongly on the structure ofthe macromolecule and its microphase separation. Polymericmicelles were first proposed as drug carriers by Bader et al. in1984.208 From the viewpoint of a fundamental understanding ofamphiphilicbehaviour, amphiphilic block copolymers possessseveral special characteristics that derive from their polymericnature. In contrast to low molecular weight amphiphiles, frag-ments of block copolymers are large enough so that many aspectsof the interactions with solvents or among chains can be under-stood in universal terms that transcend the specific chemicalnatures of the species involved. Some of the unique features ofsuperamphiphiles over small amphiphiles are entropic elasticityof random coils, nonideal free energy of mixing, excluded volume,the possibility of systematically varying the molecular weight ofhomologous series of a block copolymer and the possibility offorming greater size interfacial structures/zones.209

Amphiphilic polymers can be synthesized by introducinghydrophilic groups such as hydroxyl, carboxyl, amine, glycol,and hydrophilic polymers such as poly(ethylene glycol) (PEG),poly(vinyl alcohol), polyacrylamide, polyacrylic acids, hydroxyethyl methacrylate, poly vinyl pyridine, and poly vinyl pyrroli-done into a hydrophobic moiety. Because of their ability toform micelles, amphiphilic block copolymers are strong candi-dates for potential applications as emulsifiers, dispersants,

foamers, thickeners, rinse aids, and compatibilizers and arealso widely being used in cosmetic, detergent and foodindustries.

In solution these amphiphilic block copolymers usually havea core–shell structure with the hydrophobic block forming thecore and the hydrophilic block or blocks forming the shell.Recent pharmaceutical research on polymeric micelles hasbeen mainly in copolymers having an A–B diblock structurewith A, the hydrophilic corona and B, the hydrophobic poly-mers (core), respectively. Here we focus on their assembly andapplication on solid surfaces. Recent interests in developingamphiphilic polymer coated surfaces are twofold: (a) to improve thebiocompatibility of polymeric materials by changing the interfacialproperties of the material for obtaining non-thrombogenic surfacesand (b) to develop antifouling surface coatings.

4.3.1. Superamphiphiles as biomaterials and artificial bio-implants. As described above, polymers behave as amphiphileespecially when they have hydrophilic and hydrophobic moieties.Not limited to typical amphiphilic polymers, many syntheticpolymers show amphiphile-like properties and functionsbecause different moieties within a single polymer have differentaffinities to surrounding media. These polymers are well used inmany functions such as biological applications. For example,synthetic polymers are widely used in fabrication of artificialbio-implants either to repair or replace organs that range fromcardiac stents to dental, vascular, spine, artificial skin andorthopaedic implants. Introduction of these foreign syntheticmaterials into living tissue leads to some unwanted reactions(commonly known as side effects) such as, adsorption ofdifferent proteins and adhesion of cells.210 Above all, when apolymer surface is implanted in the blood stream, e.g. a heartstent, adsorption of blood proteins will occur that will ultimatelylead to blood clotting (thrombosis).211 The properties of theinterface between the polymer and the biological environmentare key for controlling/eliminating the fatal blood clotting.Therefore, it is of great importance for biomaterial scientiststo improve the biocompatibility of polymeric materials whilemaintaining requisite mechanical strength, flexibility andchemical resistance of the polymer.

Polymeric surfaces with low interfacial energies to water orblood are ideal for developing non-thrombogenic surfaces.Hydrophilic homopolymers such as poly(ethylene oxide)(PEO) coated substrates show reduced protein adsorption andcell adhesion.212 In contrast to the PEO coated hydrophilicsurfaces, developing a hydrophilic surface by coating smallamphiphilic molecules does not exhibit any reduction inprotein or cell adsorption. Therefore, it has been suggestedthat the excluded volume effects and rapid conformationalchanges of the water-soluble PEO chains at the surface withits high degree of hydration give rise to a low interfacial energy,which effectively reduces the hydrophobic interactions respon-sible for the protein adsorption.213 However, surface adsorbedPEO homopolymers suffer from poor stability on surfaces thatthey are adsorbed. Several techniques have been employed toimprove the stability of PEO on surfaces. One approach is tocovalently link PEO on surfaces (PEO brushes), which however,

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limits the choice of surface that can be covalently bound withthe modified PEO.214 An alternative route to produce PEOsurfaces with greater stability, and still use the adsorptiontechnique, is adsorption of amphiphilic polymers containingPEO as the hydrophilic component.215 The amphiphilic polymersmay be block or graft copolymers and, in either case, the hydro-phobic segments of the copolymers will adsorb strongly at thesubstrate surface leaving the hydrophilic flexible PEO segmentsextending outwards from the surface.

Freij-Larsson et al. have investigated the adsorption beha-viour of a number of PEO containing amphiphilic copolymerson hydrophobized silica model surfaces.216 Subsequently, theyhave studied the adsorption of serum proteins such as albuminand fibrinogen using ellipsometry. The morphology and com-position of the modified surfaces were studied using X-rayphotoelectron spectroscopy (XPS) and AFM, and contact anglemeasurements were performed to determine their wettabilitycharacteristics. A combination of hydrophobic interactionswith the substrate and a low solubility of the hydrophobicsegments of the polymers in the aqueous solution drives theamphiphilic polymers to adsorb on the hydrophobized silicasurface. The adsorbed amphiphilic polymers are suggested tobe present at the hydrophobic surface as molecularly dispersedmolecules and as micellar aggregates of different sizes, according toAFM. Although the amphiphilic polymers may not completely coverthe substrate surface, highly hydrated PEO segments extend into thesolution and sterically prevent the adsorption of serum proteinsfrom closely approaching the hydrophobic surface.

The effect on the cell response of the presence and density ofbioactive ligands on biomaterial surfaces is under frequentinvestigation. Biomaterials for guided tissue regeneration andtissue engineering are required to have well-defined surfaces thatwould provide for controlled cell–biomaterial interactions.217

Numerous strategies have been developed and are underfurther investigation for coupling of bioactive compounds topolymers for drug delivery and tissue engineering.218 Amongthe biodegradable polymers in the tissue-engineering field,aliphatic polyesters, such as polylactide (PLA), polyglycolide(PGA), polycaprolactone (PCL), and their copolymers are themost often studied.219 These polymers are easy to process,biodegradable, nontoxic and serve as 3D scaffolds. The disadvan-tage of these polymers is that they are hydrophobic in nature andthus easily fouled by proteins as discussed earlier. For the past fewdecades, the materials science community has fine tuned theproperties of antifouling surface coatings that are resistant tononspecific protein adsorption. In this regard, amphiphilicpolymers that contain PEG, phosphazene or zwitterionic smallamphiphiles have been explored in detail.220 In polyesters,due to their low content of suitable reactive groups, physicalimmobilization of hydrophilic components, such as PEO, isneeded to carry functional groups to bind bioactive compo-nents to the chain end group. Tresohlava et al. have developed amodel system using PLA surfaces modified with mixtures ofcopolymers composed of a neutral PLA-b-PEO and its analoguewith biotin at the end of PEO block where the biotin serves as asurrogate of a bioactive peptide group.221

4.3.2. Applications in anti-biofouling and biomedical ima-ging. Preventing biofouling in a marine environment is criticalbut challenging due to the amphiphilic nature of severalmarine species.222 Thus, designing a single coating that iscapable of resisting bioadhesion remains an explorativeresearch area that also includes synthesis and assembly ofamphiphilic materials. Towards this end, a number of researchgroups have demonstrated the usefulness of ethylene glycols(hydrophilic) and fluoropolymers (hydrophobic). Coatings con-taining these two materials have been shown to be effective inminimizing adhesion of a variety of marine organisms. Whileearly strategies have relied primarily on tuning the coating’schemical composition, recent developments in the field haverevealed that combating adsorption of biomass onto man-madesurfaces requires not only control over the coating’s surfacechemistry but also tailoring of its topography, charge, mobilityof the surface groups, and mechanical properties. Genzer andcoworkers have explored the possibility of using amphiphiliccopolymers comprising ethylene glycol and fluorinated groupsby chemically ‘fluorinating’ poly(2-hydroxyethyl methacrylate)(PHEMA) brushes anchored to flat solid surfaces. Post-poly-merization reaction at the hydroxyl termini of HEMA’s pendantgroups was performed using three classes of fluorinatingagents, including organosilanes, acyl chlorides, and trifluoro-acetic anhydride (TFAA). The ability to controllably distribute thefluorinated groups inside the polymer brushes to obtain tailormade hydrophobic surfaces with tunable wetting/bioadhesioncharacteristics was demonstrated. Systematic testing and perfor-mance evaluation against a variety of biological moieties andmarine species are still needed in order to fully understand therole of amphiphilic groups along the copolymer in governingbioadhesion.

Inorganic nanoparticles are attractive as biomedical imagingprobes. For computed tomography (CT) scanning, those inorganicnanoparticles are coated with biocompatible polymers such asPEG. These polymer coated nanoparticles surpass the limitationsof conventional iodine-based contrast agents for CT scanningthat includes short imaging time and the risk of renal toxicity.Another advantage of polymer coated nanoparticles as contrast-enhancing agents is their ability to be used in multiple modalities.Kim et al. have developed a hybrid nanoparticle, composed of ironoxide and gold nanoparticles, as a potential dual contrast agentfor CT and magnetic resonance imaging (MRI).223 They coatedthese nanoparticles with amphiphilic poly(DMA-r-mPEGMA-r-MA)[DMA, N,N-dimethylacrylamide; MA, methyl acrylate] to impartwater-dispersity and anti biofouling properties. This amphi-philic polymer enables coating on a variety of hydrophobicallymodified nanomaterials making the surfaces hydrophilic andresistant to nonspecific adsorption of biological species. Thisbiomaterial, poly(DMA-r-mPEGMA-r-MA), contains a hydrophilicPEG moiety, enabling the particles to disperse in water (thusshowing antibiofouling properties), and a long hydrophobicalkyl chain, enabling the polymer to coat oleylamine-stabilizedhybrid nanoparticles via hydrophobic and van der Waals inter-actions. As shown in Fig. 11, the amphiphilic polymer coatedhybrid nanoparticles show one or more iron oxide nanoparticles

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that are fused to Au nanoparticles in a bent or pyramidal shapewithout aggregation. Intravenous injection of the hybrid nano-particles into hepatoma-bearing mice results in high contrastbetween the hepatoma and normal hepatic parenchyma in bothCT and MRI. These results suggest that the amphiphilic poly-mer coated Au-Fe3O4 hybrid nanoparticles may be useful asCT/MRI dual contrast agents for in vivo hepatoma imaging.

4.4. Polyelectrolyte–amphiphile complexes

The concept of self-assembly has been successfully used toconstruct periodic nanostructures from ordered arrays oforganic molecules. Highly ordered nanostructures are to beutilized in such a way that new materials will have, at least intheory, useful physical properties for everyday applications.Polyelectrolyte complexes are being explored as a material forconstructing ordered organic molecule-periodic nanostructureswith a periodicity of 5 nm. A polyelectrolyte complex contains apolyelectrolyte and an ionic amphiphile of opposite chargeand the formation of polyelectrolyte–amphiphile complexes ismodular. Permutation and combination of amphiphiles andpolyelectrolytes is possible as either the polyelectrolyte or theamphiphiles used in the building blocks can be of either anatural or a synthetic origin. Polyethyleneimine, polyaminoacids and DNA are examples of polyelectrolytes, while typicalrepresentatives of useful amphiphiles are carboxylic acids andlipids. Interdisciplinary efforts involving physical chemistry,synthetic expertise, and colloidal science are in place to designand investigate polylectrolyte–amphiphile complexes.

Polymer complexes formed by polyelectrolytes and fluorinatedamphiphilic (PEFA) materials are the fluoro-containing analoguesof the non-fluorinated solid polyelectrolyte–amphiphile com-plexes.224 The various properties of PEFAs and non-fluorinatedpolyelectrolyte–amphiphile complexes are comparable to thoseof the classical polymers, polytetrafluoroethylene (PTFE) andpolyethylene. A common property of PEFA and polyelectrolyte–surfactant complexes (PE–surfs) is a pronounced tendency toform well-ordered liquid crystal-like structures with a highmechanical and thermal stability. The main difference is intheir wetting behaviour: PEFA forms on highly oleophobicsurfaces, while PE–surfs form on oleophilic surfaces.

A cooperative ‘zipper’ mechanism between a polyelectrolytechain and oppositely charged fluorinated amphiphilic mole-cules is postulated for the formation of the PEFA complex.

An idealized lamellar mesomorphous complex structure with arepeat unit length of d consisting of fluoroalkyl-containingsheets with a thickness of d1 (dark shaded) and ionic sheetscontaining polyelectrolytes with a thickness of d2 are formed.This multi-lamellar structure is typical of many fluorinatedPEFA materials. The molecular arrangement at the interfacecomplex to air is dominated by the enrichment of CF3-groups.The amphiphiles are strongly linked to the polyelectrolytechains, which lie about 1 nm beyond the CF3-layer.

The systematic preparation of low energy surfaces formed bythe self-assembly of PEFA is potentially of high technologicalimportance as easy-to-clean surface coatings. These coatingsare easy to prepare and are being used as thin protectivecoatings for walls that are frequently graffitized. Polyelectrolytecomplexes are also currently being used in the textile industriesas anti-soiling coatings and in sports equipment as colloidalsubstitutions.

4.5. Amphiphilic assemblies for/in mesoporous materials

The role of amphiphile self-assembly in developing a widerange of high quality mesoporous materials is imperative. Inparticular, syntheses of mesoporous materials using amphi-phile assemblies are now conducted by a large body of research-ers. These materials are defined as porous materials with porediameters in the range of 2–50 nm according to IUPAC classi-fication. The archetypal mesoporous silica materials can beprepared by silica formation about template micelle assembliesfollowed by removal of the template by appropriate methodssuch as calcination.225,226 Replica synthesis using mesoporoussilica results in extension of this family of materials to othermesoporous structures such as mesoporous carbon227–231 andcarbon nanocages.232–235 Hierarchic assembly of mesoporousmaterials has been accomplished through LbL assembly ofmesoporous materials.236–240 These advanced structures allessentially originate from amphiphile assembly. Detailed descrip-tions of typical mesoporous materials have been given in otherreviews241–244 while examples of amphiphile assemblies areshown below.

Porous inorganic oxide membranes composed of alumina ortitania that are prepared by an anodization process generallypossess packed arrays of columnar pores ranging from tensto hundreds of nanometres in diameter depending on theanodizing conditions.245 The channel direction of the columnarpore is perpendicular to the membrane surface. The orientationof these nanochannels can be controlled to obtain a requiredorientation by introducing precursor materials that contain amixture of an amphiphile (CTAB) and a silica source tetraethylorthosilicate (TEOS). The precursor is introduced into the aluminapores and the silica–amphiphile nanocomposite assembles at thepore walls to form the amphiphile-templated nanochannels.Using this simple procedure, a novel method for obtainingthe desired mesoporous materials for separation of moleculeswas demonstrated. Additionally, this methodology could alsobe used to fabricate arrays of chips by patterning of the silica–amphiphile nanocomposite in the alumina membrane leadingto special sensor array systems based on mesoporous materials.

Fig. 11 An example of hybrid nanoparticles (Au and Fe3O4) coated withamphiphilic polymers and amphiphilic molecules.

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This strategy can also be extended to other porous systems thatcontain columnar pores, for example, polycarbonate and por-ous silicon membranes. In the coming years, this methodologywill have a significant influence on the separation and catalysisindustries and on microchip technologies.

Fluorocarbons and hydrocarbons are thermodynamicallyimmiscible. Phase separation of F- and H-chain amphiphileswas first examined by Kunitake and others in micellar systems,bilayer membranes, and in liposomes.246–248 Mixed monolayersof F- and H-chain amphiphiles phase separate into patchdomains on planar surfaces. Interestingly, on curved surfaces,such as on nanoparticles, this patchy phase evolves into anequilibrium-striped phase as demonstrated by Sing et al.The Flory–Huggins interaction parameter determines the mis-cibility of two amphiphiles and their morphology and kineticsof pattern formations.249

Electron spin resonance (ESR) spectroscopy has been usedfor the study of mixed monolayers composed of hydrocarbonand fluorocarbon amphiphilic thiolates decorated with term-inal PEG chains. Apart from ESR, several other indirect meth-ods such as NMR, SERS and fluorescence tagging have beenused to understand the organization of mixed amphiphiles onsolid surfaces, particularly on nanoparticles.250–253 However,these indirect methods suffer from the lack of a general view ofthe monolayer organization. For direct visualization of mono-layer assemblies, techniques such as STM, AFM or XRD arecurrently applied.254,255 Nonetheless, there exist a number ofexperimental challenges for direct visualization including thesize of the amphiphile which is limited to 14–16 carbon atoms,rigidity of the ligands, size of the nanoparticles, and so on.Recently, Posocco et al. have presented a combined experi-mental/simulation approach to the characterization of Aunanoparticles decorated with immiscible amphiphiles of ahybrid nature, i.e., F- and H-based thiolates bearing a PEGchain as an end group.256 According to this study, the phasesegregation between H-chains and F-chains and the differentlength of the hydrophilic chains determine a peculiar folding ofthe PEG moieties responsible for the increased affinity of anorganic compound for the fluorinated region, which increasesas the size of the fluorinated domains decreases independentlyof the shape of the domains. In other words, the spontaneousorganization of the F-/H-chains in the inner part of the mono-layer is transferred to the outer surface of the nanoparticle. Bytuning the hydrocarbon and fluorocarbon chain ratio in amixed monolayer system one can effectively guide the amphi-philic assemblies in 3-D space.

5. Assembly at dynamic interfaces

Amphiphilic molecules naturally adsorb at air/water or liquid/liquid interfaces to form a monolayer. At the air/water interface,depending on the solubility characteristics of the monolayerthey are categorized either as Gibbs monolayers (a soluble mono-layer, made from relatively small hydrocarbon-tailed amphiphiles)or Langmuir monolayers (an insoluble monolayer, usuallymade from long-tailed hydrocarbon or double-tailed lipids).

Amphiphilic assemblies at liquid/liquid interfaces thermo-dynamically favour the formation of isotropic dispersions oftwo immiscible liquids knows as emulsions. There are anextensive number of studies dedicated to monolayer assembliesat the air/water interface, micelle formation, emulsification,micellar structures, foamability, foam stability, vesicles etc. Alsonumerous review articles, books and book chapters dealingwith different aspects of amphiphilic assemblies at dynamicinterfaces have been published in the past few decades. Here,we focus on some of the state-of-the-art developments inamphiphile assemblies at dynamic interfaces with specificexamples of explorative research that are promising to replaceor improve some of the existing industrial materials for noveltechnological applications in the near future.

First, we will consider the self-assembly of short-tailed,micelle-forming amphiphiles at the air/water interface. Anintensive study of self-assembly of short-tailed Gibbs mono-layer forming amphiphiles has been stimulated by theirwide range of important applications as components in thecosmetics, detergents, and food industries. Apart from thesewell established industrial applications there are severalongoing research activities exploring new uses. Thus, developmentof nanomembranes exploits the self-assembly nature of organicamphiphiles. In addition, we focus on current, technologicallyrelevant developments in Langmuir monolayer studies. Finally,we conclude this section with a brief overview of the currenttrends in unconventional amphiphiles and their assemblies atdynamic interfaces and on static surfaces.

5.1. Amphiphilic assemblies for novel nanomembranes

Nanomembranes are well suited for incorporation into othermaterials and offer unique opportunities for utilizing their size-dependent properties in commercially viable products. Thefield of synthesis and fabrication of nanomembranes is expectedto burgeon to encompass a diverse range of technologicallyimportant materials. Here we review some novel and cost-effective ways of developing nanomembranes exploiting theself-assembly nature of organic amphiphiles.

5.1.1. Amphiphilic bilayers as nanomembranes. Rama-nathan et al. have developed ultrathin, dense, and cost-effectivegas–vapor separation membranes from freestanding foamfilms.257 Foam films (also known as soap films) are made upof two identical amphiphilic monolayers adsorbed at the gas/liquid interfaces which are separated by a thin aqueous core.The interactions between the two amphiphilic surfaces of thefoam film can be precisely controlled and the thickness of thecentral aqueous core determines the membrane thickness. Whenthe aqueous core thickness is low, the amphiphilic monolayersare adsorbed onto each other and steric forces stabilize themembrane. Fundamental studies on these membranes startedin early 1980s258–263 with subsequent gas permeability character-istics of the membranes being studied in detail to probe theinteractions within the film.264–267 The influence of the charge ofthe headgroup of the amphiphilic molecule, (i.e. negative chargefor SDS, positive charge for alkyltrimethylammonium halides,and no charge for nonionic polyoxyethylene and sugar-based

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amphiphiles) on the film permeability has been well investi-gated.268–271 Effects of concentration of amphiphiles, ionicstrength, temperature, applied pressure, and curvatures of thefilm are some of the other rigorously studied parameters.272–274

Muller and Krustev have convincingly demonstrated that thepermeability of a freestanding foam film can be used as asensitive tool to evaluate minute changes that occur within thefilm architecture including variation in amphiphile packingdensity as a function of distance between two adsorbed mono-layers.275 Recently it was shown that these liquid nanomem-branes can be used as gas separation membranes. CH3- andCF3-tailed amphiphiles with head groups of various polarities(positive, negative and neutral) have been used to demonstratethe usability of these easily formed nanomembranes for industrialapplications. Permeation of gases such as oxygen, nitrogen,argon, and atmospheric air has been assessed. The resultsindicate that these films can be used for size exclusion separa-tion applications. We believe that these amphiphile-basednanomembranes will soon revolutionize the related industrialprocesses either replacing or being integrating into existingpolymer-based membranes.276,277

5.1.2. Amphiphile assembly guided single crystalline nano-membranes. An approach to free-standing nanomembranefabrication was introduced by Wang et al.278 They developeda low cost process involving amphiphile assemblies to producelarge area nanomembranes at the air/water interface. In con-trast to the above examples where amphiphile assemblies ofbilayer structures are used directly as nanomembranes, Wanget al. used the Gibbs monolayers as a template for directing thegrowth of single-crystalline nanomembranes. As shown inFig. 12, an excess of soluble amphiphile, SDS in water, formsa tightly packed Gibbs monolayer at the air/water interface. Byincreasing the pH, dodecylsufate ions are formed. Zinc nitrateand hexamethylenetetramine (HMT) are added into thissolution, since they both are precursors of zinc oxide

nanostructures in aqueous solutions. In this case, the presenceof dodecylsufate (DS) ions enables the mineralization of zincions into zinc hydroxyl sulphate hydrate. At elevated tempera-ture, crystallization of zinc hydroxy dodecylsulfate occurs bothbeneath the DS ion monolayer and in the bulk solution whereDS micelles are present. The micelles have no apparent sig-nificant influence on the diffusion-controlled growth of thenanomembrane at the water surface. Dodecylsulfate ionsremain in the crystal in a tail-to-tail configuration with surfaceheads bonding with zinc ions as shown in Fig. 13. This creates alayered structure with alternating zinc hydroxide layers anddouble hydrophobic dodecylsufate layers. These nanomem-branes were then transferred onto a silicon substrate. Thesesingle crystalline nanomembranes exhibit good flexibility andintegrity while covering and remaining intact over the entiresubstrate surface. To demonstrate its application in flexibleelectronics, a flexible thin film transistor was made from thisnanomembrane and was reported to possess good n-typetransport properties. We believe that amphiphilic assemblyprovides a low-cost and large-scale synthesis and fabricationroute for development of nanomembranes and flexible devicesfrom various functional materials that is not feasible by con-ventional membrane manufacturing processes.279

5.1.3. Bio and organic nanomembranes. Biological nano-mebranes are conventionally prepared using naturally occur-ring lipids. There is increasing demand for development ofthese membranes using synthetic analogues of lipids.280

Assembly of amphiphilic block copolymers can be used todevelop biomimetic nanomembranes as has been demon-strated previously.281–283 The advantages of these biomimeticmembranes are that their properties can be easily fine tuned bysimple variation of polymer molecular weight, composition,

Fig. 12 Formation of zinc oxide nanostructures with Gibbs monolayers of SDSas a template.

Fig. 13 Growth of nanomembranes at the water surface (A) and in solution (B).

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and structure. Moreover, they have certain advantages over naturallipid membranes, for instance, the lateral diffusivity, membranethickness, elasticity and permittivity may be controlled over abroader range that can be achieved with lipid systems.

Gluing of an LB bilayer, as introduced by Regen andcoworkers, has opened up new possibilities for the developmentof high quality and robust organic nanomembranes for gasseparation (Fig. 14).284 In the gluing process, two LB monolayersare ionically cross-linked. In order to demonstrate this concept, acalix[6]arene derivative was used as the bilayer-forming, watersoluble, charged, amphiphile and poly(4-styrenesulfonate) (PSS)as the glue.285–287 These glued bilayers are ultrathin with thick-nesses of around 6 nm, although they are easy to prepare andprocess. They can be used as organic nanomembranes for gasseparation applications since they exhibit remarkable permea-tion selectivity involving He, N2 and CO2. The results indicatethat (i) the main pathway for permeation of the small Hemolecule is through the central pore of the calix[6]arenes,(ii) the main pathway for permeation of the larger CO2 and N2

molecules is through void spaces around the perimeter of thecalix[6]arenes (due to dynamic gaps and/or physical defects),(iii) the combined cross-sectional area of the central pores of thecalix[6]arenes is large relative to the dynamic gaps and/orphysical defects around their perimeter, and (iv) ionic cross-linking of the amphiphile assembly reduces the number ofdynamic gaps and physical defects that are present.288 Thegluing not only improves the quality and stability of the LB filmsbut also their permselectivity characteristics for nanomembrane-based applications.289 The role of porous and nonporous amphi-philes and the effect of counterions on gluing and gas separationhave been explored.290 Further research is needed to improve themembrane characteristics for molecular sieving applications.

5.2. Amphiphilic-assembly-assisted hybrid materials andmicrofluidic mixing

Langmuir monolayers formed at the air/water interface byinsoluble amphiphiles and biomolecules remain an excitingarea of interest for modern science and technology. Researchon Langmuir monolayers and LB films is actively pursued bymaterials scientists, nanotechnologists, physicists, chemists,

biologists and biomedical scientists and engineers because oftheir potential application in hi-tech industries, such as energy,electronics, fluidics and sensors.291,292

Langmuir monolayers with controlled shapes, sizes, andpattern alignments can be used for surface patterning andthe system is considered to be dynamically self-assembled untiltransferred onto a solid support.293,294 Dynamic and nonlinearcharacteristics have not been well addressed although anexceptional study by Ramanathan and Fischer shows that thereexist several unexplored realms of fundamental science, whichcould potentially lead to contemporary applications of thesesystems.295 For example, in lab-on-a-chip applications, it isimportant to efficiently mix all the reactants of liquid phasechemical species. At large scales, turbulent mixing can beutilized but in miniaturized devices such as in lab-on-a-chipor in micro/nanofluidic devices it is extremely difficult to achieveturbulent mixing using existing processes or techniques due tothe ultrasmall quantities of the reactants.296 Reynolds number isanother important characteristic of the efficient mixing on micro-fluidic lab-on-a-chip devices outside the turbulent regime.

Ramanathan and Fischer have proposed a solution for thisproblem by locally heating a quasi 2D Langmuir monolayer atthe air/water interface (Fig. 15).297 Local heating using an IRlaser serves as a quasi-two-dimensional pump leading to two-dimensional flow. Thermal and surface tension gradientsopen a cavitation gas bubble in the liquid expanded phase ofthe Langmuir monolayer.298 This cavitation bubble exerts athermocapillary stress that sets the liquid into motion andamplifies the displacement and flow.299,300 By compressing therigid monolayer, lipid folds are created and used to partiallyblock the flow. When the flow passes the fold for a vortex withstreamlines circling around the centre. The vortical flow in thequasi-2D system resembles eddies forming behind objects in ahigh Reynolds number flow. This is a simple way of achievingtwo-dimensional mixing through formation of vortical flow behindthe folds in a low Reynolds number Langmuir monolayer.

5.3. Current trends in unconventional amphiphiles and theirassemblies

Exploratory research and novel applications are on the increasein the field of amphiphilic copolymers and their assembly on

Fig. 14 Schematic illustration of the concept of material separation through aglued LB bilayer.

Fig. 15 Method and concept of investigation of local heating of a quasi 2DLangmuir monolayer at the air/water interface.

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static surfaces.301–304 For instance, synthesis and self-assemblyof light-sensitive photosurfactants and photopolymers havebeen briefly reviewed by Eastoe and Vesperinas.305

5.3.1. Amphiphilic polymer networks. Amphiphilic poly-mer networks represent by their diversity a class of compoundswhich are of great importance due to their unique propertiesand challenging targeted applications that conventional(homo)polymer-based hydrogels cannot provide. Indeed, asso-ciation of hydrophilic and hydrophobic segments into the samestructure confers to the final materials a set of reliable proper-ties directly related to their individual microstructures.306

These polymeric networks are finding applications as switches,sensors, actuators, bioreactors, separation systems and drugdelivery systems. Many synthetic approaches are still availablefor exploration. As has been pointed out by Mespouille et al. intheir review article, ‘‘ongoing advances in polymer synthesis andmechanism understanding will complete the palette of toolsaccessible to polymer scientists to reach more and more complexstructures as cross-linked materials in their diversities’’.307

5.3.2. Amphiphilic homopolymers. The origin of amphi-philicity of a hydrophilic/lipophilic block copolymer is quiteunderstandable where as the amphiphilicity of a hompolymer iscounter-intuitive.308 Thayumanavan and coworkers have recentlydeveloped a molecular design based on homopolymers in whichboth the hydrophilic and the hydrophobic moieties are incorporatedwithin the monomer unit.309,310 Here the molecular level conforma-tional changes in each monomer unit are amplified to exhibittransformation from micelle-like assembly into reverse micelle-likeassembly and vice versa depending on the solvent environment.Such assemblies from a homopolymer and their reversibilities areunique. The interior of these micelles was used as nanocontainersto carry out organic photochemical reactions. Interestingly, theselectivity in amphiphilic homopolymer nanocontainers is muchhigher than those obtained with micellar containers based on blockcopolymers or small molecule amphiphiles. This is an exciting areaof development which offers potential for explorative studies as wellas for chemical and biochemical applications.311

5.3.3. Amphoteric amphiphiles. Amphoteric amphiphilescontain two charged groups of different polarity (i.e. positiveor negative). Whereas the positive charge is almost alwaysammonium, the source of the negative charge may vary (carboxy-late, sulphate, sulphonate). Solubility of an amphiphile in aqueoussolution is influenced by the charge on the polar head group.Generally, anionic amphiphiles are soluble from neutral to higherpH, cationic amphiphiles are soluble from very low to neutral pH.Nonionic amphiphiles are soluble around neutral pH. Amphotericamphiphiles feature the intrinsic ability to change in charge fromcationic via zwitterionic (net uncharged) to anionic going fromlow to high pH. They function well in high electrolyte formula-tions and are compatible with all other classes of amphiphiles.Their excellent dermatological properties make them particularlysuited for use in personal care and household cleaning products.Most amphoteric amphiphiles are used in baby shampoosbecause they are gentle and do not cause painful irritation tothe eyes. By far the most commonly used is cocamidopropylbetaine, or occasionally cocamido betaine.

An important property of the amphoterics is the ionizationstate of their molecules, which is dependent on the pH of thesolution. Alargova et al. have studied the dissociation of theamphiphile ionizable groups, as well as the association of ionsfrom the solution to the ionizable groups of the amphotericadsorption layer.312 They have shown that the ionization stateof the amphoteric amphiphile turns out to be markedly differentwhen the molecule is in the bulk of the solution and when it isincorporated into an adsorption monolayer. Since amphotericspossess both positive and negative charges, they are soluble atalmost any pH with minimal solubility at their isoelectric point,which is normally around neutral pH.313

5.3.4. Giant amphiphiles. Macromolecular amphiphileswith a hydrophobic polymer tail and a protein head-group,i.e. giant amphiphiles are a relatively new class of biohybridcompounds. In principle, a giant amphiphile is a diblockcopolymer possessing a protein as one of the two polymerblocks. Giant amphiphiles can be formed by direct covalentattachment of the polymer to the protein, e.g. by a cycloadditionreaction or a reaction with a SH group on the surface ofthe protein.314–317 Biotinylated poly(N-isopropylacrylamide)–streptavidin protein hybrid is a good example of giant amphiphiles.Further studies in giant amphiphiles are directed at investigatingthe influence of different polymer tails (i.e., polystyrenes of differentlengths with different hydrophilic spacer groups for attachmentto the enzyme) upon the activity and the self-assemblingbehaviour of giant amphiphiles.

5.3.5. Cleavable and switchable amphiphiles. Amphiphilesare widely used in a range of applications including emulsions,microemulsions and miniemulsion polymerizations, separations,and recovery and transportation of oils in the petrochemicalindustries. In these applications, emulsions are used either foran efficient heat transfer or to lower the oil/water interfacialtension. Hence, the emulsions are only useful during one stageof the process after which the cleaning of the system of thestabilizing amphiphiles is cumbersome. The problem of how todeal with the ‘‘temporary emulsions’’ that are desired only duringone stage of a process remains a challenge. One approach toaddress this issue is to develop a new class of amphiphiles thatare cleavable or switchable. A cleavable amphiphile will possessa cleavable functional group such as an ester between thehydrophilic head group and the hydrophobic tail.318 By theapplication of a chemical or photochemical trigger the cleavableamphiphile can be irreversibly converted into one or more mole-cules with greatly reduced surface activity.

In contrast to cleavable amphiphiles which undergo irreversiblechanges, switchable amphiphiles undergo fully reversible inter-conversions between active and inactive forms. Additionaladvantages of switchable amphiphiles are that their activitycan be delayed until required, they can be recovered and reusedafterward, and their removal from the product stream can befacilitated by switching the amphiphile to form least soluble inthe relevant medium. Different types of triggers have been useddepending on the functional groups used in the cleavable andswitchable amphiphiles. Recently, Liu et al. have reported thatcarbon dioxide and air can be used as on and off triggers to

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reversibly transform long-chain alkyl amidine compounds intocharged amphiphiles. Self-immolative polymers are anotherdevelopment in the area of unique macromolecules that areable to react to multiple types of environmental influences withamplified response outputs.319,320 Fundamentally, this area willdevelop in the exploration of the rates of amphiphile switchingand optimization of amphiphile designs for specific applica-tions, especially in nanoparticle synthesis, polymerization, andin the oil industry.321

5.3.6. Graphene oxide (GO) sheets. Graphene oxide (GO)sheets consist of a single atomic layer of sp2-hybridized carbonatoms derivatized by phenol hydroxyl and epoxide groups.These functional groups are mainly located on the basal planeand ionizable carboxylic acid groups are located at the edges asshown in Fig. 16. Jiaxing Huang and coworkers were the firstto demonstrate the amphiphilic nature of GOs.322–324 Thesurfactant-like properties of GO sheets can be used to assemblethem controllably at interfaces by tuning their amphiphilicity.This 2D (unconventional) amphiphile is becoming a key com-ponent in the field of materials science and engineering.

5.3.7. Nanoparticles as amphiphiles. Kramer and coworkershave shown that the surface chemistry of nanoparticles can bemodified so that these particles behave like amphiphiles and canbe localized at the interfaces between two fluids.325 In their recentwork, they have shown that nanoparticles can act as amphiphilesfor block copolymers, leading to stable bicontinuous morpholo-gies with characteristic domain sizes of less than 100 nm. Theyhave systematically varied the volume fraction of the nanoparticleamphiphiles using a method that involves blending symmetric ABdiblock copolymers with amphiphile nanoparticles whose sur-faces are treated to promote strong binding to the A/B interfaceswhile avoiding macrophase separation. This method has implica-tions for a variety of applications that require a continuous phasefor the transport of molecular species, ions, or electrons and asecond phase for the mechanical support or the conduction of a

separate species. Furthermore, the materials that can be fabri-cated using this method are potentially enhanced by theelectrical, optical, magnetic, and/or catalytic properties of theinorganic nanoparticles incorporated into the bicontinuousstructure.

With regard to the fabrication and controlled assemblyof amphiphilic nanoparticles several strategies have beenused.326 One among them is the ‘‘bricks and mortar’’ strategywhere nanoparticles act as bricks while amphiphilic ligands(surfactants or polymers) act as mortars. This process is com-prehensively summarized in Fig. 17 and in the review article byRotello and coworkers.327

Hu et al. have demonstrated that the Janus type biphasic,anisotropic nanoparticles can be prepared using a template-freesynthetic process by exploiting the cooperative, multidentategold nanoparticle binding with amphiphilic triblock copolymerpoly(ethylene oxide)-b-poly(lipoic acid 2-hydroxy-3-(metha-cryloyloxy)-propyl ester-co-glycidyl methacrylate)-b-polystyrene(PEO-b-P(LAMP-co-GMA)-b-PS) (Fig. 18).328 In this amphiphilicblock copolymer the middle block binds to the nanoparticleswhile the two outer blocks exert steric hindrance. Sincethe hydrophobic Au nanoparticles hybrid middle block issandwiched between PEO and PS outer blocks, the Au nano-particles would be expected to locate at the interface betweenthe hydrophilic PEO and hydrophobic PS domains within theblock copolymer’s self-assembled nanostructures. Thus, theas-synthesized Au nanoparticle hybrid amphiphilic triblockcopolymers have the potential to self-assemble into variousmorphologies, including hybrid micelles, (branching) rods,vesicles, and large compound micelles (LCMs), in aqueous media.This exploration of synthesis and self-assembly of nanoparticlesat dynamic interfaces is attractive as it is a promising wayfor scale-up productions of highly efficient monofunctionalizedultrasmall anisotropic nanoparticles.

Fig. 16 Various patterns of functional group distributions on the surface ofgraphene oxide nano sheets.

Fig. 17 The ‘bricks and mortar’ strategy for nanocomposite formation wherenanoparticles act as bricks while amphiphilic ligands (surfactants or polymers) actas mortars.

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A similar template-free method was reported by Niikuraet al. who used semifluorinated oligo(ethylene glycol) ligandson o20 nm Au nanoparticle surfaces.329 In this case solvophobicinteractions of fluorinated bundles are exploited to form sub-100 nmnanoparticle vesicles. These self-assembled hollow vesicular struc-tures are of considerable interest in many fields ranging frommaterials sciences to biophysics and nanomedicine.330,331 However,unlike their molecular analogues, amphiphiles incorporating nano-scopic, inorganic cores allow for additional functionalities such assuperparamagnetism, plasmonic excitation, and enhanced fluores-cence, amongst others.332–334

In general, all the examples discussed above depend onnon-covalent interactions such as dipole–dipole, electrostatic,van der Waals, hydrogen bonding, and hydrophobic inter-actions are largely used to dictate the self-assembly process.Another approach to develop amphiphilic nanoparticles is bygrafting two chemically distinct (hydrophobic and hydrophilic)polymers. The nanoparticles grafted with a mixed hydrophobicand hydrophilic brush are analogous to block copolymers as awhole. This creates a new type of hybrid building block inheritingthe amphiphilicity-driven self-assembly of block copolymers toform vesicular structures. Here the covalently anchored polymergrafts provide a means of modulating the interparticle couplingthrough their conformational changes. Both ‘‘grafting-to’’ and‘‘grafting-from’’ approaches can be used to develop amphiphilicjanus nanoparticles.335 Judicious selection of polymers could leadto directed assembly of nanoparticles into complex structures fortargeted applications.336 If the grafted polymers are responsiveto external stimulus then this approach can be potentially usedfor sensing and delivery applications as it was alluded by Duanand coworkers.337 Besides vesicular structures, by making useof directional interactions amphiphilic nanoparticles can beassembled into higher order aggregates, including well-definedclusters, disk-shaped and cylindrical micelles, colloidosomes,and lattices.338–348

Andala et al. have recently described a simple and reliablemethod to produce inorganic nanoparticles functionalized

asymmetrically with domains of hydrophilic and hydrophobicligands on their respective hemispheres.349 This is a thermo-dynamically controlled, spontaneous process, in which theparticle cores and two competing ligands assemble atthe interface between two immiscible liquids to reduce theinterfacial energy. Results from this explorative study suggestthat this functionalization strategy is not limited to photonic(Au) materials but should instead be applicable to any nano-particle systems for which chemical ligation methods are welldeveloped. To prove this hypothesis, magnetic amphiphilesof iron oxide nanoparticles were prepared using hydrophobic(1,2-decanediol, DCD) and hydrophilic (dihydrocinnamic acid,DCA; fully deprotonated at pH = 11) diol ligands. Assembly ofthese particles at the liquid–liquid interface is another area ofemerging research.

Park and Lee have studied the equilibrium configuration(i.e., orientation and vertical displacement with respect tothe interface) of nonspherical amphiphilic particles withasymmetric geometry and asymmetric wetting propertiesat the oil–water interface.350 Their results indicate that theorientation behaviour of amphiphilic ellipsoids at the interfacestrongly depends on the aspect ratio, the location of thewettability separation line, and the surface wettability of eachside of the particles. Conversely, in the case of amphiphilicdumbbells, the coexistence of upright/tilted orientations wasnot observed in their phase diagram. This intermediate behaviouris unique to these asymmetric amphiphilic dumbbells and hasnot been observed in symmetric Janus dumbbells. Liquid–liquidinterfaces can be used as a template to assemble asymmetricamphiphilic nanoparticles to form tunable suprastructures bycontrolling the particle–particle interactions at the fluid–fluidinterface.351,352

6. Advanced topics from simulation toapplication

As described above, amphiphile assemblies are formed throughrather simple and universal mechanisms. Therefore, theseassemblies can be of a great variety and some of the mostattractive examples cannot be easily categorized. In this section,uncategorized examples from recent research are summarized.

6.1. Theoretical, modeling and simulation studies onamphiphile assemblies

Developing a thorough fundamental understanding of amphi-philes is the first step in designing novel amphiphiles and advancedapplications. There are several fundamental questions the answersto which will allow scientists the capability to design novelamphiphiles tuned to maximize the efficiency of the intendedprocess or application. Some of these fundamental questionsinclude, how do amphiphile characteristics such as relativenumbers of hydrophilic and hydrophobic groups, their arrange-ment in the molecule, bond angle, and branching affect thestructure of the interface, and how does this structure affectinterfacial tension? A number of experimental techniques and

Fig. 18 Janus type biphasic, anisotropic nanoparticles with amphiphilic triblockcopolymers for further formation of hybrid nanostructures.

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instruments have been developed to probe the structure ofinterfacial systems such as neutron scattering, thin film pressurebalance, surface tension meter, and sum-frequency spectroscopy.

Theoretical studies such as molecular simulations, atomisticmolecular dynamic simulations, coarse grained moleculardynamics simulations, and more recently the mesoscale simula-tion techniques have been used to study interfacial systems.353–364

These studies help us to understand the detailed structure ofamphiphilic monolayers at a fluid interface, to establish bulkamphiphile concentrations, to obtain detailed physical insightinto liquid–liquid interfaces, and to study the effect of bulkamphiphile concentration on interfacial tension. Second-orderclassical density functional theory has also been applied to assessthe effect of amphiphilic properties on the interfacial structureand interfacial tension of a planar oil/water interface. Specifically,the effect of the relative locations of the hydrophobic and hydro-philic portions, rigidity vs. flexibility, and bond angle of theamphiphile are exemplified using this approach. The secondorder density functional theory (DFT) studies demonstrate thatbond angle and branching significantly affect the tendency of anamphiphile to adsorb on the interface and the degree to which theinterfacial tension is lowered.

6.2. Amphiphilic assemblies in higher dimensions

Amphiphiles naturally self-assemble into 2D structures at inter-faces as discussed earlier for Gibbs and Langmuir monolayers.These can be further processed to obtain 2D assemblies eitherby LB deposition or by applying excess surface pressure. Insolution at the fluid/fluid interface, 3D assemblies in the formof lamellar vesicles, micelles, and other pseudodimensionalstructures are also seen. There have been considerable effortsmade to design 3D nanostructures utilizing the self-assemblycharacteristics of the amphiphiles with exact precision.365

Drumund and co-workers have shown that small amphiphilicmolecules self-assemble into periodic 3D geometries in proticionic liquids and polar molecular solvents.366–370

Naturally occurring dipeptides such as l-carnosine (b-alanine-histidine, bAH) has a range of biological activities in the muscleand brain tissues of humans and other vertebrates at relativelyhigh concentrations. These are highly water-soluble dipeptidesthat do not naturally have the ability to self-assemble in water.Castelletto, Hamely and others have been exploring variousstrategies for the construction of novel bAH supramolecular self-assemblies to expand the potential biochemical activities of thispeptide particularly for regenerative medicine applications.371–373

One such approach is to induce fibrillization of bAH using astructure-directing agent. An alternative strategy to drive bAH self-assembly involves turning the dipeptide into a peptide amphi-phile (PA) by the lipidation of bAH.374 It has been shown thatself-assembly of lipid-bAH is driven by the hydrophobicity of thelipidating chain to form stacked layered structures of so callednanotapes. In nanotapes, bilayers are found to coexist withmonolayers in which the PA molecules pack with alternatingup–down arrangement so that the headgroups decorate bothsurfaces. The bilayers become dehydrated as PA concentrationincreases and the number of layers in the stack decreases to

produce ultrathin nanotapes comprising 2–3 bilayers. Addingthe PA to dipalmitoylphosphatidylcholine (DPPC) multilamellarvesicles induces a transition to well-defined unilamellar vesiclesand it is noteworthy that the C16-bAH does not self-assemble intofibers in the presence of DPPC. This may be due to the DLVOtype electrostatic interactions between DPPC head groups andpeptide amphiphile assemblies that may effectively screenelectrostatic repulsions.

Studies on the self-assembly of helical structures are motivatedby their biological and technological importance.375 Biopolymerssuch as double helix nucleic acids, a-helix proteins and somepolysaccharides are chiral in nature. Cellular membranes arecomposed of chiral amphiphiles such as phospholipids andcholesterols though the membrane itself is achiral. Syntheticamphiphiles have exhibited distinct helical or twisted struc-tures. Shimizu and Masuda were the first to show thatthe formation of chiral assemblies from the viewpoint of theeven–odd effect of the connecting links and reported internalmolecular arrangements of the self-assembled fibers fromdumbbell-shaped bolaamphiphiles.376

Recently, Liu et al. have demonstrated a method to engineerthe self-assembly of supra-amphiphiles based on dual chargetransfer interactions.377 With this approach they could program thetransformation of well-defined 1D nanosheets into 2D nanofibers.The directional charge transfer interactions of naphthalenediimideand naphthalene were used to form H-shaped supra-amphiphiles.Subsequently, these H-supra amphiphiles were complexed withpyrene derivatives as shown in Fig. 19. This line of researchinvolving rational design and fabrication of dimensionally-controlled organic nanostructures will become a key researcharea in the field of macromolecular nanomaterials.

6.3. Multi-stimuli-responsive amphiphiles and theirassemblies

Amphiphiles and their assemblies that are responsive toexternal stimuli are of considerable interest due to theirrole in developing technologically smart materials for use in

Fig. 19 H-shaped supra-amphiphiles and their nanostructure formation.

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various industrial applications. In particular, stimuli-responsiveamphiphilic polymers have been studied in detail as they canself-assemble into various architectures that can accommodateguest molecules and release them upon triggering by anexternal stimuli. Light, temperature, pH, redox potentials,and solvents have been used as stimuli, largely in micellarsystems. Until recently only a single stimulus had been used.378

Developments in the design and synthesis of novel blockcopolymers have enabled a new class of polymeric amphiphilesthat are responsive to more than one stimulus. Dual-stimuli-responsive block copolymers that respond to pH and tempera-ture or salinity have been reported.379–383 The lower criticalsolution temperature (LCST) of the proline derivatives wastuned between 18 and 55 1C by varying the pH.

Thayumanavan and coworkers have recently introduced afacile synthetic method for the synthesis of block copolymerslinked via disulphide functionality for developing a triplestimuli sensitive polymeric system.384 The design involves twoblocks in which one block is sensitive to temperature while theother block is sensitive to pH. The novelty of this design comesfrom the disulphide linker that not only connects those twosensitive blocks but also itself is sensitive to redox conditions.If the two sensitive blocks are amphiphilic in nature then onewould envisage a supramolecular assembly that can respond tochanges in temperature, pH and redox potential as shown inFig. 20. Serial and parallel responses to multiple stimuli havealso been demonstrated for encapsulation and release of hydro-phobic guest molecules. As indicated elsewhere, these multiple-stimulus response systems have the prospect of being morebroadly applied in fields such as controlled release, catalysis,and separation.

For biomedical applications, the design of multi-responsive-amphiphiles that are biocompatible is desirable. Besides devel-oping new amphiphilic polymers that respond to multipletriggers, there is also considerable work in progress aimedat biomedical applications where responses to uncommonstimuli, which are inherently present in living systems, arerequired. Such stimuli include antigen–antibody interactions,

enzymes, sugars, external fields such as light, electric, magneticand sonic fields. For additional details refer to the review articleby Sumerlin and coworkers.385 The control of amphiphilestabilized foams is very important in foods and cosmeticswhere controlled stability is needed in wastewater treatment,froth floating processes, etc. For example, antifoaming agentsmay be used to irreversibly break the foam bubbles.386

6.4. Amphiphile assembly with nanostructured materials

The partitioning of wormlike micelles between a bulk solutionand nanopores can be controlled by tuning the amphiphile–wall interactions (Fig. 21).387 Self-assembly of a common non-ionic amphiphile in tubular 8 nm nanopores is tuned bycoadsorption of the amino acid lysine, which reducesthe adsorption affinity for the amphiphile. An evolution ofequilibrium morphologies of the amphiphile aggregates asa function of the level of surface modification y wasfound using in situ small-angle neutron scattering (SANS),which is free from artifacts that can arise during the dryingprocess prior to electron microscopy. At low lysine adsorptionlevels, the amphiphile formed patchy bilayer aggregates atthe pore walls, as observed in the absence of lysine. Atthe highest degree of surface modification (y = 0.9), theamphiphile was excluded from the pore space and formedwormlike micelles in the aqueous bulk phase, reminiscentof size exclusion of polymers from narrow pores withnonadsorbing walls.

Graphene is the state-of-the-art material for several fieldsbecause of its unique electrical, mechanical, and thermalcharacteristics.388–391 There are various ways to produce gra-phene but one of them is by the use of ultrasonic exfoliation. Inthis process, amphiphiles are used to lower the liquid/vapourinterfacial energy of the solution to an optimum range thatcorresponds to the energy required to separate the graphitesheets beyond the range of the van der Waals forces. Moreover,the amphiphile adsorbs onto the exfoliated graphene sheetsthat creates an extra repulsive force which would prevent there-aggregation of the graphene sheets. Depending on the amphi-phile and the influence on the change in surface tension as afunction of concentration, different concentrations of graphenein suspension have been produced. By continuously replacingthe amphiphile to lower the surface tension during sonicationand the production of the graphene surface area, the concentrationof particles was significantly increased. Cationic, anionic, andnonionic amphiphiles were studied and all showed significantincreases in the concentration of graphene produced usingthis continuous addition method.392

6.5. Amphiphile-assemblies in energy applications

Amphiphile assemblies play a vital role in energy technolo-gies.393–396 One direct example is their significant role inpetroleum industries for enhanced oil recovery using the frothflotation process. In this process, an ultralow interfacialtension is one of the most important criteria. Alkane carbonnumbers and equivalent alkane carbon numbers of severalhydrocarbon, hydrocarbon mixtures using amphiphiles of the

Fig. 20 Block copolymers linked via disulphide functionality for the triple stimulisensitive polymeric system.

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same structural type have been an important recent subject ofresearch.397 Effects of various electrolytes and temperature oninterfacial tensions of alkylbenzene sulfonate amphiphile solu-tions were investigated by Cao et al.398

In hybrid solar cells semiconducting nanoparticles such asCdSe, Cds, Pbs, TiO2 and ZnO are used as acceptors (in theplace of fullerenes) in bulk heterojunction photovoltaicdevices. Band-gap tunability of these semiconducting nano-particles and a wide selection of geometries (rods, tripods,spheres) make them attractive as acceptor materials. Coatingthese semiconducting nanoparticles with non-semiconductingamphiphiles enables suppression of fast recombination butdoes not hinder the efficient quenching of excitons by chargetransfer. Thus, the quantum efficiency can be improved byselecting the appropriate nanoparticle–amphiphile combi-nation, which could further improve the power conversionefficiency of the device.399

6.6. Applications in advanced biological and clinical systems

Amphiphile self-assemblies have been traditionally used tomimic bio-membranes. Fundamental studies on these modelsystems are directly related to interactions in lung membraneswith surrounding fluids, oxygen transport/permeation throughlung membranes, lipid–lipoprotein interactions with cellmembranes, etc. The biotechnological aspects of amphiphileassembly science are becoming an increasingly large area.Recently, Lindman and coworkers have provided detailedinsight into condensation of DNA by cationic amphiphiles(Fig. 22).400 They showed that with an increasing concentrationof CTAB, condensation of the DNA precedes macroscopic phaseseparation where a charge neutral precipitate forms. Further-more, while mixing DNA with an excess of CTAB, positivelyovercharged mixed aggregates were formed.401

A lipoprotein contains both proteins and lipids (amphiphile)that are bound to the proteins. The major function of lipopro-teins is to transport lipids/fats such as triacylglycerols (glycerolesterified with three fatty acids, or triglycerides) around thebody in the bloodstream, which allows fats to move through thewater inside and outside cells. Since different lipoproteinscontain different amounts of triglycerides and cholesterol,they may be separated by centrifuging them as particles with

different densities, including low-density (LDL), high-density(HDL), and very low-density (VLDL) particles. Structurally theselipoprotein particles have hydrophilic groups of phospholipids,cholesterol, and apoproteins directed outward, as shownin Fig. 23.402 This structural arrangement solubilizes theselipoproteins in the salty, aqueous blood. Presently, there arenumerous explorative research projects probing the usability ofthis natural self-assembly of bio-amphiphiles for clinicalapplications.403

In particular, the disposition of hydrophobic drugs in theaqueous environment of the blood is thermodynamically unfa-vourable and the use of self-assembled lipoproteins for targeteddrug delivery (of lipophilic drugs) has become a key focus inrecent years. For over a decade, Kishore Wasan and coworkershave experimentally investigated the roles of lipids andlipoproteins in modifying the biological activity of water-insoluble drugs.404 They have deduced the potential mechan-isms by which water-insoluble drugs interact with lipids andlipoproteins and how these interactions impact on the absorp-tion, distribution, efficacy, toxicity and metabolism of suchcompounds. Elucidation of the mechanisms that dictatedrug–lipoprotein association and blood-to-tissue partitioningof lipoprotein-encapsulated drugs might yield valuable insightinto the factors governing the pharmacological activity andpotential toxicity of these compounds.

Fig. 21 Self-assembly of a nonionic amphiphile in tubular nanopores.

Fig. 22 Aggregate formation from DNA coils and CTAB for DNA delivery to cell.

Fig. 23 Lipoprotein particles with hydrophilic groups of phospholipids, choles-terol, and apoproteins directed outward.

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7. Short summary and message

This perspective summarizes research efforts on assembliesand properties of amphiphiles from their basic properties torecent advanced examples. Although amphiphiles have simplestructures when compared with other biological componentssuch as proteins, polysaccharides, and nucleic acids, the struc-tural variety of their assemblies is immense. Complex mole-cules such as proteins perform specialized tasks and can formonly predesignated structures that can be energetically welldefined. In contrast, amphiphiles have only a few structuralcharacteristics, solvophilic or solvophobic, and can form variousstable and/or metastable structures depending on surroundingsolution or interfacial conditions. Using these less complex mole-cules we can design and prepare a great variety of assembledstructures with well-organized internal nanostructures. It could besaid that amphiphiles including surfactants and lipids are the bestbuilding blocks for biological nanoarchitectonics. In amphiphilenanoarchitectonics, component structures are simple whileassembled structures are complex. Applications based on thesestructures may be realized by applying our accumulated knowledgeand understanding amphiphile design, characterization, analyses,interpretation and theoretical predictions based on physicalchemistry and chemical physics. In addition, fusion of fields ofemerging biomaterial assemblies405,406 and advanced evaluationtechniques407,408 would further open many possibilities.

Acknowledgements

Partial support from the Center for Nanophase MaterialsSciences, which is sponsored at Oak Ridge National Laboratoryby the Scientific User Facilities Division, Office of Basic EnergySciences, U.S. Department of Energy is greatly acknowledged.This work was also partly supported by World Premier Inter-national Research Center Initiative (WPI Initiative), MEXT,Japan and the Core Research for Evolutional Science andTechnology (CREST) program of Japan Science and TechnologyAgency (JST), Japan.

Notes and references

1 M. C. Daniel and D. Astruc, Chem. Rev., 2004, 104, 293.2 Z. L. Wang, Mater. Sci. Eng., R, 2009, 64, 33.3 T. Hino, T. Hasegawa, K. Terabe, T. Tsuruoka, A. Nayak,

T. Ohno and M. Aono, Sci. Technol. Adv. Mater., 2011,12, 013003.

4 S. Wu, T. Tsuruoka, K. Terabe, T. Hasegawa, J. P. Hill,K. Ariga and M. Aono, Adv. Funct. Mater., 2011, 21, 93.

5 T. Hasegawa, K. Terabe, T. Tsuruoka and M. Aono, Adv.Mater., 2012, 24, 252.

6 K. Ariga, J. P. Hill, M. V. Lee, A. Vinu, R. Charvet andS. Acharya, Sci. Technol. Adv. Mater., 2008, 9, 014109.

7 K. Sakakibara, J. P. Hill and K. Ariga, Small, 2011, 7, 1288.8 M. Li, S. Ishihara, Q. Ji, M. Akada, J. P. Hill and K. Ariga,

Sci. Technol. Adv. Mater., 2012, 13, 053001.

9 M. Ramanathan, S. M. Kilbey II, Q. Ji, J. P. Hill andK. Ariga, J. Mater. Chem., 2012, 22, 10389.

10 M. Ramanathan, Y.-C. Tseng, K. Ariga and S. B. Darling,J. Mater. Chem. C, 2013, 1, 2080.

11 S. Acharya, B. Das, U. Thupakula, K. Ariga, D. D. Sarma,J. Israelachvili and Y. Golan, Nano Lett., 2013, 13, 409.

12 K. Ariga, J. P. Hill and Q. Ji, Macromol. Biosci., 2008, 8, 981.13 K. Ariga, Q. Ji, J. P. Hill, N. Kawazoe and G. Chen, Expert

Opin. Biol. Ther., 2009, 9, 307.14 K. Ariga, Q. Ji and J. P. Hill, Adv. Polym. Sci., 2010, 229, 51.15 E. Ruiz-Hitzky, M. Darder, P. Aranda and K. Ariga, Adv.

Mater., 2010, 22, 323.16 P. Guo, Nat. Nanotechnol., 2010, 5, 833.17 K. Ariga, M. McShane, Y. M. Lvov, Q. Ji and J. P. Hill, Expert

Opin. Drug Delivery, 2011, 8, 633.18 K. Ariga, Q. Ji, T. Mori, M. Naito, Y. Yamauchi, H. Abe and

J. P. Hill, Chem. Soc. Rev., DOI: 10.1039/C2CS35475F.19 D. J. McClements, E. A. Decker, Y. Park and J. Weiss, Crit.

Rev. Food Sci. Nutr., 2009, 49, 577.20 D. Kitamoto, T. Morita, T. Fukuoka, M. Konishi and

T. Imura, Curr. Opin. Colloid Interface Sci., 2009, 14, 315.21 I. Kralova and J. Sjoblom, J. Dispersion Sci. Technol., 2009,

30, 1363.22 V. S. Balachandran, S. R. Jadhav, P. K. Vemula and G. John,

Chem. Soc. Rev., 2013, 42, 427.23 G. S. Hartley, Aqueous Solutions of Paraffinic-Chain Salts.

A Study of Micelle Formation, Herman, Paris, 1936.24 This terminology was first proposed by Dr Masakazu Aono

at 1st International Symposium on NanoarchitectonicsUsing Suprainteractions (NASI-1) at Tsukuba in 2000.

25 P. S. Weiss, ACS Nano, 2007, 1, 379.26 K. Ariga, M. V. Lee, T. Mori, X.-Y. Yu and J. P. Hill, Adv.

Colloid Interface Sci., 2010, 154, 20.27 K. Ariga, M. Li, G. J. Richards and J. P. Hill, J. Nanosci.

Nanotechnol., 2011, 11, 1.28 M. Aono, Y. Bando and K. Ariga, Adv. Mater., 2012,

24, 150.29 K. Ariga, Q. Ji, M. J. McShane, Y. M. Lvov, A. Vinu and

J. P. Hill, Chem. Mater., 2012, 24, 728.30 K. Ariga, S. Ishihara, H. Abe, M. Li and J. P. Hill, J. Mater.

Chem., 2012, 22, 2369.31 K. Ariga, Q. Ji, J. P. Hill, Y. Bando and M. Aono, NPG Asia

Mater., 2012, 4, e17.32 T. Mori, K. Sakakibara, H. Endo, M. Akada, K. Okamoto,

A. Shundo, M. V. Lee, Q. Ji, T. Fujisawa, K. Oka,M. Matsumoto, H. Sakai, M. Abe, J. P. Hill and K. Ariga,Langmuir, DOI: 10.1021/la304293z.

33 Y. Ishikawa, H. Kuwahara and T. Kunitake, J. Am. Chem.Soc., 1994, 116, 5579.

34 H. Kuwahara, M. Hamada, Y. Ishikawa and T. Kunitake,J. Am. Chem. Soc., 1993, 115, 3002.

35 N. Kimizuka, T. Kawasaki, K. Hirata and T. Kunitake, J. Am.Chem. Soc., 1995, 117, 6360.

36 T. Kawasaki, M. Tokuhiro, N. Kimizuka and T. Kunitake,J. Am. Chem. Soc., 2001, 123, 6792.

37 K. Katagiri, K. Ariga and J. Kikuchi, Chem. Lett., 1999, 661.

PCCP Perspective

Publ

ishe

d on

05

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13. D

ownl

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/201

6 15

:11:

26.

View Article Online



38 K. Katagiri, R. Hamasaki, K. Ariga and J. Kikuchi, Langmuir,2002, 18, 6709.

39 K. Katagiri, R. Hamasaki, K. Ariga and J. Kikuchi, J. Am.Chem. Soc., 2002, 124, 7892.

40 Q. Zhang, K. Ariga, A. Okabe and T. Aida, J. Am. Chem. Soc.,2004, 126, 988.

41 W. Otani, K. Kinbara, Q. Zhang, K. Ariga and T. Aida,Chem.–Eur. J., 2007, 13, 1731.

42 K. Katagiri, M. Hashizume, K. Ariga, T. Terashima andJ. Kikuchi, Chem.–Eur. J., 2007, 13, 5272.

43 I. W. Hamley, Introduction to Soft Matter: Polymers, Colloids,Amphiphiles and Liquid Crystals, John Wiley & Sons, Ltd.,2000.

44 J. N. Israelachvili, D. J. Mitchell and B. W. Ninham,J. Chem. Soc., Faraday Trans. 2, 1976, 72, 1525.

45 P. J. Missel, N. A. Mazer, G. B. Benedek, C. Y. Young andM. C. Carey, J. Phys. Chem., 1980, 84, 1044.

46 G. Porte and J. Appell, J. Phys. Chem., 1981, 85, 2511.47 B. Kachar, D. F. Evans and B. W. Ninham, J. Colloid Inter-

face Sci., 1984, 100, 287.48 H. Kunieda, J. Colloid Interface Sci., 1989, 114, 378.49 H. Kunieda, K. Shigeta and M. Suzuki, Langmuir, 1999,

15, 3118.50 L. K. Shrestha, M. Masaya, T. Sato, D. P. Acharya,

T. Iwanaga and H. Kunieda, Langmuir, 2006, 22, 1449.51 L. K. Shrestha, R. G. Shrestha and K. Aramaki, J. Dispersion

Sci. Technol., 2009, 287, 1305.52 H. Rehage and H. Hoffmann, J. Phys. Chem., 1988, 92, 4712.53 P. K. Vinson, J. R. Bellare, H. T. Davis, W. G. Miller and

L. E. Scriven, J. Colloid Interface Sci., 1991, 142, 74.54 D. Danino, Y. Talmon, H. Levy, G. Beinert and R. Zana,

Science, 1995, 269, 1420.55 S. R. Raghavan and E. W. Kaler, Langmuir, 2001, 17, 300.56 C. A. Dreiss, Soft Matter, 2007, 3, 956.57 R. G. Shrestha, L. K. Shrestha and K. Aramaki, J. Colloid

Interface Sci., 2007, 311, 276.58 L. K. Shrestha, T. Sato and K. Aramaki, J. Phys. Chem. B,

2007, 111, 1664.59 L. K. Shrestha, Y. Yamamoto, S. Arima and K. Aramaki,

Langmuir, 2011, 27, 2340.60 L. K. Shrestha, R. G. Shrestha and K. Aramaki, Langmuir,

2011, 27, 5862.61 L. K. Shrestha, R. G. Shrestha, M. Abe and K. Ariga, Soft

Matter, 2011, 7, 10017.62 L. K. Shrestha, T. Sato, R. G. Shrestha, J. Hill, K. Ariga and

K. Aramaki, Phys. Chem. Chem. Phys., 2011, 13, 4911.63 N. T. Southall, K. A. Dill and A. D. J. Haymet, J. Phys. Chem.

B, 2002, 106, 521.64 D. Chandler, Nature, 2005, 437, 640.65 R. Nagarajan and E. Ruckenstein, Langmuir, 1991, 7, 2934.66 L. J. Chen, S. Y. Lin and C. C. Huang, J. Phys. Chem. B, 1998,

102, 4350.67 H. Kunieda, K. Nakamura and A. Uemoto, J. Colloid Inter-

face Sci., 1992, 150, 235.68 H. Kunieda, K. Ozawa and K. L. Huang, J. Phys. Chem. B,

1998, 102, 831.

69 M. T. Hai, H. X. Han, G. Y. Yang, H. K. Yan and Q. Y. Han,Langmuir, 1999, 15, 1640.

70 H. Kunieda, M. Horii, M. Koyama and K. Sakamoto,J. Colloid Interface Sci., 2001, 236, 78.

71 K. Ozawa, U. Olsson and H. Kunieda, J. Dispersion Sci.Technol., 2001, 22, 119.

72 M. Kahlweit and R. Strey, Angew. Chem., Int. Ed. Engl., 1985,24, 654.

73 M. Abe, T. Yamazaki, K. Ogino and M. J. Kim, Langmuir,1992, 8, 833.

74 H. Kunieda and M. Yamagata, Langmuir, 1993, 9, 3345.75 H. Kunieda, A. Nakamo and M. A. Pes, Langmuir, 1995,

11, 3302.76 S. S. Funarit, M. C. Holmes and G. J. T. Tiddy, J. Phys.

Chem., 1992, 96, 11029.77 S. S. Funarit, M. C. Holmes and G. J. T. Tiddy, J. Phys.

Chem., 1994, 98, 3015.78 C. E. Fairhurst, M. C. Holmes and M. S. Leaver, Langmuir,

1996, 12, 6336.79 S. S. Funari and G. Rapp, J. Phys. Chem. B, 1997, 101, 732.80 P. Sakya, J. M. Seddon, R. H. Templer, R. J. Mirkin and

G. J. T. Tiddy, Langmuir, 1997, 13, 3706.81 C. E. Fairhurst, M. C. Holmes and M. S. Leaver, Langmuir,

1997, 13, 4964.82 Y. Nibu and T. Inoue, J. Colloid Interface Sci., 1998,

205, 305.83 M. Leaver, A. Fogden, M. C. Holmes and C. Fairhurst,

Langmuir, 2001, 17, 35.84 R. Dong and J. Hao, Chem. Rev., 2010, 110, 4978.85 L. J. Magid, J. Phys. Chem. B, 1998, 102, 4064.86 M. Gobe, K. Kon-no, K. Kandori and A. Kitahara, J. Colloid

Interface Sci., 1983, 93, 293.87 K. Kurihara, J. Kizling, P. Stenius and J. H. Fendler, J. Am.

Chem. Soc., 1983, 105, 2574.88 J. Penfold, E. Staples, I. Tucker and P. Cummins, J. Colloid

Interface Sci., 1997, 185, 424.89 Md. H. Uddin, C. Rodriguez, K. Watanabe, M. A. Lopez-

Quintela, T. Kato, H. Furukawa, A. Harashima andH. Kunieda, Langmuir, 2001, 17, 5169.

90 C. Rodriguez, Md. H. Uddin, K. Watanabe, H. Furukawa,A. Harashima and H. Kunieda, J. Phys. Chem. B, 2002,106, 22.

91 L. K. Shrestha, T. Sato, D. P. Acharya, T. Iwanaga, K. Aramakiand H. Kunieda, J. Phys. Chem. B, 2006, 110, 12266.

92 L. K. Shrestha, M. Dulle, O. Glatter and K. Aramaki,Langmuir, 2010, 26, 7015.

93 J. C. Ravey, M. Buzier and C. Picot, J. Colloid Interface Sci.,1984, 97, 9.

94 P. Debye and H. Coll, J. Colloid Sci., 1962, 17, 220.95 R. C. Little and C. R. Singleterry, J. Phys. Chem., 1964,

68, 3453.96 R. C. Little, J. Colloid Interface Sci., 1966, 21, 266.97 K. Kon-no, H. Asano and A. Kitahara, Prog. Colloid Polym.

Sci., 1983, 68, 20.98 N. M. Correa, J. J. Silber, R. E. Riter and N. E. Levinger,

Chem. Rev., 2012, 112, 4569.

Perspective PCCP

Publ

ishe

d on

05

Apr

il 20

13. D

ownl

oade

d by

Uni

vers

ita d

i Pad

ova

on 2

6/04

/201

6 15

:11:

26.

View Article Online



99 H. F. Eicke and H. Christen, J. Colloid Interface Sci., 1974,48, 281.

100 D. Attwood and C. M. McDonald, Colloid Polym. Sci., 1974,252, 138.

101 T. H. Ibrahim and R. D. Neuman, Langmuir, 2004, 20, 3114.102 S.-H. Tung, Y.-E. Huang and S. R. Raghavan, J. Am. Chem.

Soc., 2006, 128, 5751.103 S.-H. Tung, Y.-E. Huang and S. R. Raghavan, Langmuir,

2007, 23, 372.104 R. Kumar, A. M. Ketner and S. R. Raghavan, Langmuir,

2010, 26, 5405.105 K. Hashizaki, T. Chiba, H. Taguchi and Y. Saito, Colloid

Polym. Sci., 2009, 287, 927.106 K. Hashizaki, H. Taguchi and Y. Saito, Colloid Polym. Sci.,

2009, 287, 1099.107 H. Kunieda and K. Shinoda, J. Colloid Interface Sci., 1980,

75, 601.108 H. Kunieda and K. Shinoda, J. Dispersion Sci. Technol.,

1982, 3, 233.109 S. E. Friberg, I. Blute, H. Kunieda and P. Stenius, Langmuir,

1986, 2, 659.110 H. Kunieda, C. Solans and J. L. Parra, Colloids Surf., 1987,

24, 225.111 C. Solans, R. Pons, S. Zhu, H. T. Davis, D. F. Evans,

K. Nakamura and H. Kunieda, Langmuir, 1993, 9, 1479.112 T. K. De and A. Maitra, Adv. Colloid Interface Sci., 1995,

59, 95.113 R. E. Riter, J. R. Kimmel, E. P. Undiks and N. E. Levinger,

J. Phys. Chem. B, 1997, 101, 8292.114 J. P. Cason and C. B. Roberts, J. Phys. Chem. B, 2000,

104, 1217.115 Q. Li, T. Li and J. Wu, J. Phys. Chem. B, 2000, 104, 9011.116 M. Kanamaru and Y. Einaga, Polymer, 2002, 43, 3925.117 L. K. Shrestha, T. Sato and K. Aramaki, Langmuir, 2007,

23, 6606.118 L. K. Shrestha and K. Aramaki, J. Dispersion Sci. Technol.,

2007, 28, 1236.119 L. K. Shrestha and K. Aramaki, J. Oleo Sci., 2009, 58, 235.120 L. K. Shrestha, R. G. Shrestha, D. Varade and K. Aramaki,

Langmuir, 2009, 25, 4435.121 L. K. Shrestha, O. Glatter and K. Aramaki, J. Phys. Chem. B,

2009, 113, 6290.122 L. K. Shrestha, T. Sato and K. Aramaki, Phys. Chem. Chem.

Phys., 2009, 11, 4251.123 L. K. Shrestha, R. G. Shrestha and K. Aramaki, J. Nanosci.

Nanotechnol., 2011, 11, 4863.124 J. N. Israelachvili, Intermolecular and Surface Forces,

Academic Press, London, 1985.125 J. H. Fendler, Membrane Mimetic Chemistry, Wiley,

New York, 1983.126 R. Langer, Science, 1990, 249, 1527.127 A. Memoli, L. G. Palermiti, V. Travagli and F. Alhaique,

J. Soc. Cosmet. Chem., 1993, 44, 123.128 A. Memoli, L. G. Palermiti, V. Travagli and F. Alhaique,

J. Soc. Cosmet. Chem., 1994, 45, 167.129 G. Gregoriadis, Trends Biotechnol., 1995, 13, 527.

130 I. F. Uchegbu and S. P. Vyas, Int. J. Pharm., 1998, 172, 33.131 D. E. Discher and A. Eisenberg, Science, 2002, 297, 967.132 N. E. Gabriel and M. F. Roberts, Biochemistry, 1984,

23, 4011.133 Y. Talmon, D. F. Evans and B. W. Ninham, Science, 1983,

221, 1047.134 J. E. Brady, D. F. Evans, B. Kachar and B. W. Ninham, J. Am.

Chem. Soc., 1984, 106, 4279.135 W. R. Hargreaves and D. W. Deamer, Biochemistry, 1978,

17, 3759.136 E. W. Kaler, A. K. Murthy, B. E. Rodriguez and J. A. N.

Zasadzinski, Science, 1989, 245, 1371.137 H. Kunieda, K. Nakamura and D. F. Evans, J. Am. Chem.

Soc., 1991, 113, 1051.138 H. Kunieda, K. Nakamura, H. t. Davis and D. F. Evans,

Langmuir, 1991, 7, 1915.139 H. Kunieda, M. Akimaru, N. Ushio and K. Nakamura,

J. Colloid Interface Sci., 1993, 156, 446.140 H. Kunieda, S. Makino and N. Ushio, J. Colloid Interface

Sci., 1991, 147, 286.141 H. Mollee, J. D. Vrind and T. D. Vringer, J. Pharm. Sci.,

2000, 89, 930.142 C. Boettcher, B. Schade and J. H. Fuhrhop, Langmuir, 2001,

17, 873.143 D. Dominguez-Gutierrez, M. Surtchev, E. Eiser and

C. J. Elsevier, Nano Lett., 2006, 6, 145.144 S. H. Tung, H. Y. Lee and S. R. Raghavan, J. Am. Chem. Soc.,

2008, 130, 8813.145 A. Ulman, Chem. Rev., 1996, 96, 1533.146 S. K. Arya, P. R. Solanki, M. Datta and B. D. Malhotra,

Biosens. Bioelectron., 2009, 24, 2810.147 T. Michinobu, S. Shinoda, T. Nakanishi, J. P. Hill, K. Fujii,

T. N. Player, H. Tsukube and K. Ariga, J. Am. Chem. Soc.,2006, 128, 14478.

148 S. Acharya, A. Shundo, J. P. Hill and K. Ariga, J. Nanosci.Nanotechnol., 2009, 9, 3.

149 S. Acharya, J. P. Hill and K. Ariga, Adv. Mater., 2009, 21, 2959.150 T. Mori, K. Okamoto, H. Endo, J. P. Hill, S. Shinoda,

M. Matsukura, H. Tsukube, Y. Suzuki, Y. Kanekiyo andK. Ariga, J. Am. Chem. Soc., 2010, 132, 12868.

151 K. Ariga, S. Ishihara, H. Izawa, H. Xia and J. P. Hill, Phys.Chem. Chem. Phys., 2011, 13, 4802.

152 T. Michinobu, S. Shinoda, T. Nakanishi, J. P. Hill, K. Fujii,T. N. Player, H. Tsukube and K. Ariga, Phys. Chem. Chem.Phys., 2011, 13, 4895.

153 K. Ariga, T. Mori and J. P. Hill, Soft Matter, 2012, 8, 15.154 K. Ariga, T. Mori and J. P. Hill, Adv. Mater., 2012, 24, 158.155 K. Ariga, H. Ito, J. P. Hill and H. Tsukube, Chem. Soc. Rev.,

2012, 41, 5800.156 K. Sakakibara, L. A. Joyce, T. Mori, T. Fujisawa,

S. H. Shabbir, J. P. Hill, E. V. Anslyn and K. Ariga, Angew.Chem., Int. Ed., 2012, 51, 9643.

157 K. Ariga, J. P. Hill and Q. Ji, Phys. Chem. Chem. Phys., 2007,9, 2319.

158 Q. Ji, I. Honma, S.-M. Paek, M. Akada, J. P. Hill, A. Vinuand K. Ariga, Angew. Chem., Int. Ed., 2010, 49, 9737.

PCCP Perspective

Publ

ishe

d on

05

Apr

il 20

13. D

ownl

oade

d by

Uni

vers

ita d

i Pad

ova

on 2

6/04

/201

6 15

:11:

26.

View Article Online



159 M. Li, S. Ishihara, M. Akada, M. Liao, L. Sang, J. P. Hill,V. Krishnan, Y. Ma and K. Ariga, J. Am. Chem. Soc., 2011,133, 7348.

160 K. Ariga, Y. M. Lvov, K. Kawakami, Q. Ji and J. P. Hill, Adv.Drug Delivery Rev., 2011, 63, 762.

161 H. Wang, S. Ishihara, K. Ariga and Y. Yamauchi, J. Am.Chem. Soc., 2012, 134, 10819.

162 Z. Adamczyk and P. Weronski, Adv. Colloid Interface Sci.,1999, 83, 137.

163 L. Boinovich, Curr. Opin. Colloid Interface Sci., 2010, 15, 297.164 J. Brinck, B. Jonsson and F. Tiberg, Langmuir, 1998,

14, 1058.165 D. A. Woods, J. Petkov and C. D. Bain, J. Phys. Chem. B,

2011, 115, 7341.166 D. A. Woods, J. Petkov and C. D. Bain, J. Phys. Chem. B,

2011, 115, 7353.167 Y. Chevalier, Curr. Opin. Colloid Interface Sci., 2003, 7, 3.168 E. Blomberg, R. Verrall and P. M. Claesson, Langmuir,

2008, 24, 1133.169 M. Ferrari, Self-Assembly of Surfactants at Solid Surfaces.

Supramolecular Chemistry: From Molecules to Nanomater-ials, John Wiley & Sons, 2012.

170 R. Xing and S. E. Rankin, J. Phys. Chem. B, 2006, 110, 295.171 S. Yang and M. G. Khaledi, Anal. Chem., 1995, 67, 499.172 J. Sjodahl, Å. Emmer, B. Karlstam, J. Vincent and

J. Roeraade, J. Chromatogr., B: Biomed. Sci. Appl., 1998,705, 231.

173 P. Boivin, R. K. Kobos, S. L. Papa and W. H. Scouten,Biotechnol. Appl. Biochem., 1991, 14, 155.

174 H. J. Barraza, M. J. Hwa, K. Blakley, E. A. O’Rear andB. P. Grady, Langmuir, 2001, 17, 5288.

175 O. J. Rojas, L. Macakova, E. Blomberg, Å. Emmer andP. M. Claesson, Langmuir, 2002, 18, 8085.

176 P. M. Claesson and H. K. Christenson, J. Phys. Chem., 1988,92, 1650.

177 H. K. Christenson, P. M. Claesson, J. Berg and P. C. Herder,J. Phys. Chem., 1989, 93, 1472.

178 T. Tsuzuki, Int. J. Nanotechnol., 2009, 6, 567.179 T. Trindade, P. O’Brien and N. L. Pickett, Chem. Mater.,

2001, 13, 3843.180 I. Matsui, J. Chem. Eng. Jpn., 2005, 38, 535.181 C. N. R. Rao, H. S. S. Ramakrishna Matte, R. Voggu and

A. Govindaraj, Dalton Trans., 2012, 41, 5089.182 Y.-W. Jun, J.-S. Choi and J. Cheon, Angew. Chem., Int. Ed.,

2006, 45, 3414.183 N. Gaponik, D. V. Talapin, A. L. Rogach, A. Kornowski,

A. Eychmueller and H. Weller, Nano Lett., 2002, 2, 803.184 Y. Yin and A. P. Alivisatos, Nature, 2005, 437, 664.185 S. G. Kwon, Y. Piao, J. Park, S. Angappane, Y. Jo,

N. M. Hwang, J. G. Park and T. Hyeon, J. Am. Chem. Soc.,2007, 129, 12571.

186 C. B. Murray, C. R. Kagan and M. G. Bawendi, Annu. Rev.Mater. Sci., 2000, 30, 545.

187 E. V. Shevchenko, D. V. Talapin, H. Schnablegger,A. Kornowski, O. Festin, P. Svedlindh, M. Haase andH. Weller, J. Am. Chem. Soc., 2003, 125, 9090.

188 D. V. Talapin, J.-S. Lee, M. V. Kovalenko and E. V. Shevchenko,Chem. Rev., 2010, 110, 389.

189 M. P. Pileni, B. W. Ninham, T. Gulik-Kryzwicki, J. Tanori,I. Lisiecki and A. Filankembo, Adv. Mater., 1999, 11, 1358.

190 S. Link, M. B. Mohamed and M. A. El–Sayed, J. Phys. Chem.B, 1999, 103, 3073.

191 X. G. Peng, L. Manna, W. D. Yang, J. Wickham, E. Scher,A. Kadavanich and A. P. Alivisatos, Nature, 2000, 404, 59.

192 D. G. Shchukin and G. B. Sukhorukov, Adv. Mater., 2004,16, 671.

193 C. J. Murphy and N. R. Jana, Adv. Mater., 2002, 14, 80.194 J. Gao, C. M. Bender and C. J. Murphy, Langmuir, 2003,

19, 9065.195 B. Nikoobakht and M. A. El-Sayed, Chem. Mater., 2003,

15, 1957.196 J. J. Choi, C. R. Bealing, K. Bian, K. J. Hughes, W. Zhang,

D. M. Smilgies, R. G. Hennig, J. R. Engstrom andT. Hanrath, J. Am. Chem. Soc., 2011, 133, 3131.

197 C. R. Bealing, W. J. Baumgardner, J. J. Choi, T. Hanrathand R. G. Hennig, ACS Nano, 2012, 6, 2118.

198 M. Li, H. Schnablegger and S. Mann, Nature, 1999,402, 393.

199 R. A. Sperling and W. J. Parak, Philos. Trans. R. Soc., A,2010, 368, 1333.

200 A. Filankembo and M. P. Pileni, J. Phys. Chem. B, 2000,104, 5865.

201 Z. Nie, D. Fava, E. Kumacheva, S. Zou, G. C. Walker andM. Rubinstein, Nat. Mater., 2007, 6, 609.

202 M. P. Pileni, Nat. Mater., 2003, 2, 145.203 B. L. Cushing, V. L. Kolesnichenko and C. J. O’Connor,

Chem. Rev., 2004, 104, 3893.204 C. Burda, X. Chen, R. Narayanan and M. A. El-Sayed, Chem.

Rev., 2005, 105, 1025.205 J. A. Dahl, B. L. S. Maddux and J. E. Hutchison, Chem. Rev.,

2007, 107, 2228.206 A. R. Tao, S. Habas and P. Yang, Small, 2008, 4, 310.207 A. Zabet-Khosousi and A. A. Dhirani, Chem. Rev., 2008,

108, 4072.208 H. Bader, H. Ringsdorf and B. Schmidt, Angew. Makromol.

Chem., 1984, 123, 457.209 M. Tirrell, S. Patel and G. Hadziioannou, Proc. Natl. Acad.

Sci. U. S. A., 1987, 84, 4725.210 F. Silver and C. Doillon, Biocompatibility Interactions of

Biological and Implantable Materials, VCH Publishers,New York, 1989, vol. 1, pp. 1–24.

211 E. Ruckenstein and S. V. Gourisankar, J. Colloid InterfaceSci., 1984, 101, 436.

212 S. I. Jeon, J. H. Lee, J. D. Andrade and P. G. DeGennes,J. Colloid Interface Sci., 1991, 142, 149.

213 Y. Mori, S. Nagaoka, H. Takiuchi, T. Kikuci, N. Noguchi,H. Tanzawa and Y. Noishili, Trans. Am. Soc. Artif. lntern.Organs, 1982, 28, 459.

214 C. Freij-Larsson and B. Wesslen, J. Appl. Polym. Sci., 1993,50, 345.

215 J. Lee, J. H. Kopecek and J. D. Andrade, J. Biomed. Mater.Res., 1989, 23, 351.

Perspective PCCP

Publ

ishe

d on

05

Apr

il 20

13. D

ownl

oade

d by

Uni

vers

ita d

i Pad

ova

on 2

6/04

/201

6 15

:11:

26.

View Article Online



216 C. Freij-Larsson, T. Nylander, P. Jannasch and B. Wesslen,Biomaterials, 1996, 17, 2199.

217 J. M. Goddard and J. H. Hotchkiss, Prog. Polym. Sci., 2007,32, 698.

218 S. E. Sakiyama-Elbert and J. A. Hubbell, Annu. Rev. Mater.Res., 2001, 31, 183.

219 L. G. Griffith, Acta Mater., 2000, 48, 263.220 ACS Symposium Series 680, ed. J. M. Harris and S. Zalipsky,

American Chemical Society, Washington, DC, 1997.221 E. Tresohlava, S. Popelka, L. Machova and F. Rypacek,

Biomacromolecules, 2010, 11, 68.222 S. Arifuzzaman, A. E. Ozcam, K. Efimenko, D. A. Fischer

and J. Genzer, Biointerphases, 2009, 4, FA33.223 D. Kim, M. K. Yu, T. S. Lee, J. J. Park, Y. Y. Jeong and S. Jon,

Nanotechnology, 2011, 22, 155101.224 A. F. Thuenemann, Polym Int., 2000, 49, 636.225 T. Yanagisawa, T. Shimizu, K. Kuroda and C. Kato, Bull.

Chem. Soc. Jpn., 1990, 63, 988.226 C. T. Kresge, M. E. Leonowicz, W. J. Roth, J. C. Vartuli and

J. S. Beck, Nature, 1992, 359, 710.227 S. H. Joo, S. J. Choi, I. Oh, J. Kwak, Z. Liu, O. Terasaki and

R. Ryoo, Nature, 2001, 412, 169.228 J. Lee, J. Kim and T. Hyeon, Adv. Mater., 2012, 18, 2073.229 K. K. R. Datta, B. V. Subba Reddy, K. Ariga and A. Vinu,

Angew. Chem., Int. Ed., 2010, 49, 5961.230 L. K. Shrestha, Y. Yamauchi, J. P. Hill, K. Miyazawa and

K. Ariga, J. Am. Chem. Soc., 2013, 135, 586.231 W. Chaikittisilp, K. Ariga and Y. Yamauchi, J. Mater. Chem.

A, 2013, 1, 14.232 A. Vinu, M. Miyahara, V. Sivamurugan, T. Mori and

K. Ariga, J. Mater. Chem., 2005, 15, 5122.233 K. Ariga, A. Vinu, M. Miyahara, J. P. Hill and T. Mori, J. Am.

Chem. Soc., 2007, 129, 11022.234 K. K. R. Datta, A. Vinu, S. Mandal, S. Al-deyab, J. P. Hill and

K. Ariga, J. Nanosci. Nanotechnol., 2011, 11, 3084.235 K. K. R. Datta, A. Vinu, S. Mandal, S. Al-deyab, J. P. Hill and

K. Ariga, J. Nanosci. Nanotechnol., 2011, 11, 3959.236 Q. Ji, M. Miyahara, J. P. Hill, S. Acharya, A. Vinu, S. B. Yoon,

J.-S. Yu, K. Sakamoto and K. Ariga, J. Am. Chem. Soc., 2008,130, 2376.

237 K. Ariga, A. Vinu, Q. Ji, O. Ohmori, J. P. Hill, S. Acharya,J. Koike and S. Shiratori, Angew. Chem., Int. Ed., 2008,47, 7254.

238 Q. Ji, S. B. Yoon, J. P. Hill, A. Vinu, J.-S. Yu and K. Ariga,J. Am. Chem. Soc., 2009, 131, 4220.

239 Q. Ji, S. Acharya, J. P. Hill, A. Vinu, S. B. Yoon, J.-S. Yu,K. Sakamoto and K. Ariga, Adv. Funct. Mater., 2009,19, 1792.

240 K. Ariga, Q. Ji, J. P. Hill and A. Vinu, Soft Matter, 2009,5, 3562.

241 K. Ariga, A. Vinu, J. P. Hill and T. Mori, Coord. Chem. Rev.,2007, 251, 2562.

242 Z. Li, J. C. Barnes, A. Bosoy, J. F. Stoddart and J. I. Zink,Chem. Soc. Rev., 2012, 41, 2590.

243 W. Xuan, C. Zhu, Y. Liu and Y. Cui, Chem. Soc. Rev., 2012,41, 1677.

244 K. Ariga, A. Vinu, Y. Yamauchi, Q. Ji and J. P. Hill, Bull.Chem. Soc. Jpn., 2012, 85, 1.

245 A. Yamaguchi, F. Uejo, T. Yoda, T. Uchida, Y. Tanamura,T. Yamashita and N. Teramae, Nat. Mater., 2004, 3, 337.

246 P. Mukerjee and A. Y. S. Yang, J. Phys. Chem., 1976,80, 1388.

247 T. Kunitake, S. Tawaki and N. Nakashima, Bull. Chem. Soc.Jpn., 1983, 56, 3235.

248 R. Elbert, T. Folda and H. Ringsdorf, J. Am. Chem. Soc.,1984, 106, 7687.

249 C. Singh, A. M. Jackson, F. Stellacci and S. C. Glotzer, J. Am.Chem. Soc., 2009, 131, 16377.

250 C. Gentilini, F. Evangelista, P. Rudolf, P. Franchi,M. Lucarini and L. Pasquato, J. Am. Chem. Soc., 2008,130, 15678.

251 S. Pradhan, L. E. Brown, J. P. Konopelski and S. Chen,J. Nanopart. Res., 2009, 11, 1895.

252 M. Lucarini and L. Pasquato, Nanoscale, 2010, 2, 668.253 A. Stewart, S. Zheng, M. R. McCourt and S. E. J. Bell, ACS

Nano, 2012, 6, 3718.254 A. M. Jackson, J. W. Myerson and F. Stellacci, Nat. Mater.,

2004, 3, 330.255 P. D. Jadzinsky, G. Calero, C. J. Ackerson, D. A. Bushnell

and R. D. Kornberg, Science, 2007, 318, 430.256 K. Jaskiewicz, A. Larsen, D. Schaeffel, K. Koynov,

I. Lieberwirth, G. Fytas, K. Landfester and A. Kroeger,ACS Nano, 2012, 6, 7254.

257 M. Ramanathan, H.-J. Muller, H. Mohwald and R. Krastev,ACS Appl. Mater. Interfaces, 2011, 3, 633.

258 M. Nedyalkov, R. Krustev, D. Kashchiev, D. Platikanov andD. Exerowa, Colloid Polym. Sci., 1988, 266, 291.

259 R. Krustev, D. Platikanov and M. Nedyalkov, Colloids Surf.,A, 1993, 79, 129.

260 R. Krustev, D. Platikanov and M. Nedyalkov, Colloids Surf.,A, 1997, 123, 383.

261 R. Krustev, D. Platikanov, A. Stankova and M. Nedyalkov,J. Dispersion Sci. Technol., 1997, 18, 789.

262 G. Andreatta, L. T. Lee, F. K. Lee and J. J. Benattar, J. Phys.Chem. B, 2006, 110, 19537.

263 D. Matuszak, G. L. Aranovich and M. D. Donohue, Ind. Eng.Chem. Res., 2006, 45, 5501.

264 A. C. Brown, W. C. Thuman and J. W. McBain, J. ColloidSci., 1953, 8, 508.

265 M. Blank, J. Phys. Chem., 1962, 66, 1911.266 H. M. Princen and S. G. Mason, J. Colloid Sci., 1965,

20, 353.267 H. M. Princen, J. Th. G. Overbeek and S. G. Mason,

J. Colloid Interface Sci., 1967, 24, 125.268 R. M. Muruganathan, H.-J. Muller, H. Mohwald and

R. Krastev, Langmuir, 2005, 21, 12222.269 R. M. Muruganathan, R. Krastev, H.-J. Muller and

H. Mohwald, Langmuir, 2006, 22, 7981.270 R. Farajzadeh, R. Krastev and P. L. J. Zitha, Langmuir, 2009,

25, 2881.271 R. M. Muruganathan, H.-J. Muller, K. Vedula, H. Mohwald

and R. Krastev, Colloids Surf., A, 2010, 354, 1.

PCCP Perspective

Publ

ishe

d on

05

Apr

il 20

13. D

ownl

oade

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6/04

/201

6 15

:11:

26.

View Article Online



272 R. M. Muruganathan, R. Krustev, H.-J. Muller, H. Mohwald,B. Kolaric and R. von Klitzing, Langmuir, 2004, 20, 6352.

273 P. M. Claesson, M. Kjellin, O. J. Rojas and C. Stubenrauch,Phys. Chem. Chem. Phys., 2006, 8, 5501.

274 C. Stubenrauch, O. J. Rojas, J. Schlarmann andP. M. Claesson, Langmuir, 2004, 20, 4977.

275 R. Krustev and H.-J. Muller, Langmuir, 1999, 15, 2134.276 R. Farajzadeh, A. Andrianov, R. Krastev, G. J. Hirasaki and

W. R. Rossen, Adv. Colloid Interface Sci., 2012, 183, 1.277 S. E. Friberg, Curr. Opin. Colloid Interface Sci., 2010,

15, 359.278 F. Wang, J.-H. Seo, Z. Ma and X. D. Wang, ACS Nano, 2012,

6, 2602.279 B. Nikoobakht and X. Li, ACS Nano, 2012, 6, 1883.280 D. K. Martin, Nanobiotechnology of Biomimetic Membranes,

Springer, New York, 1st edn, 2006, vol. 1, p. 182.281 M. P. Goertz, L. E. Marks and G. A. Montano, ACS Nano,

2012, 6, 1532.282 S. Belegrinou, J. Dorn, M. Kreiter, K. Kita-Tokarczyk,

E.-K. Sinner and W. Meier, Soft Matter, 2010, 6, 179.283 J. Dorn, S. Belegrinou, M. Kreiter, E.-K. Sinner and

W. Meier, Macromol. Biosci., 2011, 11, 514.284 M. Wang, V. Janout and S. L. Regen, Langmuir, 2010,

26, 12988.285 X. Yan, V. Janout, J. T. Hsu and S. L. Regen, J. Am. Chem.

Soc., 2003, 125, 8094.286 J. Li, V. Janout and S. L. Regen, Langmuir, 2006, 22, 11224.287 J. Li, V. Janout and S. L. Regen, Chem. Mater., 2006,

18, 5065.288 Y. Wang, E. Stedronsky and S. L. Regen, Langmuir, 2008,

24, 6279.289 M. Wang, V. Janout and S. L. Regen, Langmuir, 2012,

28, 4614.290 D. H. McCullough III, V. Janout, J. Li, J. T. Hsu, Q. Truong,

E. Wilusz and S. L. Regen, J. Am. Chem. Soc., 2004,126, 9916.

291 R. M. Crooks and A. J. Ricco, Acc. Chem. Res., 1998, 31, 219.292 W. N Vreeland and A. E Barron, Curr. Opin. Biotechnol.,

2002, 13, 87.293 R. Bruinsma, F. Rondelez and A. Levine, Eur. Phys. J. E: Soft

Matter Biol. Phys., 2001, 6, 191.294 L. Li, M. H. Kopf, S. V. Gurevich, R. Friedrich and L. Chi,

Small, 2012, 8, 488.295 S. V. Wegner, A. Okesli, P. Chen and C. He, J. Am. Chem.

Soc., 2007, 129, 3474.296 B. Zhao, J. S. Moore and D. J. Beebe, Science, 2001,

291, 1023.297 R. M. Muruganathan and Th. M. Fischer, J. Phys. Chem. B,

2006, 110, 22979.298 R. M. Muruganathan, Z. Khattari and Th. M. Fischer,

J. Phys. Chem. B, 2005, 109, 21772.299 R. M. Muruganathan and Th. M. Fischer, J. Phys. Chem. B,

2006, 110, 22160.300 M. Collinet-Fressancourt, L. Leclercq, P. Bauduin,

J.-M. Aubry and V. Nardello-Rataj, J. Phys. Chem. B, 2011,115, 11619.

301 H. M. Janssen, E. Peeters, M. F. van Zundert, M. H. P. vanGenderen and E. W. Meijer, Macromolecules, 1997,30, 8113.

302 P. V. Kamat and D. Meisel, Curr. Opin. Colloid Interface Sci.,2002, 7, 282.

303 A. B. Jodar-Reyes, J. L. Ortega-Vinuesa and A. Martın-Rodrıguez,J. Colloid Interface Sci., 2005, 282, 439.

304 T. Cohen-Karni, R. Langer and D. S. Kohane, ACS Nano,2012, 6, 6541.

305 J. Eastoe and A. Vesperinas, Soft Matter, 2005, 1, 338.306 G. Kali, T. K. Georgiou, B. Ivan, C. S. Patrickios, E. Loizou,

Y. Thomann and J. C. Tiller, Langmuir, 2007, 23, 10746.307 L. Mespouille, J. L. Hedrick and P. Dubois, Soft Matter,

2009, 5, 4878.308 M. Moffitt, K. Khougaz and A. I. Eisenberg, Acc. Chem. Res.,

1996, 29, 95.309 B. S. Sandanaraj, D. R. Vutukuri, J. M. Simard, A. Klaikherd,

R. Hong, V. M. Rotello and S. Thayumanavan, J. Am. Chem.Soc., 2005, 127, 10693.

310 S. Basu, D. R. Vutukuri and S. Thayumanavan, J. Am. Chem.Soc., 2005, 127, 16794.

311 S. Arumugam, D. R. Vutukuri, S. Thayumanavan andV. Ramamurthy, J. Am. Chem. Soc., 2005, 127, 13200.

312 R. G. Alargova, I. Y. Vakarelsky, V. N. Paunov,S. D. Stoyanov, P. A. Kralchevsky, A. Mehreteab andG. Broze, Langmuir, 1998, 14, 1996.

313 Amphoteric Surfactants (Surfactant Science), ed. Eric G. Lomax,CRC Press, 1996.

314 K. Velonia, A. E. Rowan and R. J. M. Nolte, J. Am. Chem.Soc., 2002, 124, 4224.

315 M. J. Boerakker, J. M. Hannink, P. H. H. Bomans,P. M. Frederik, R. J. M. Nolte, E. M. Meijer and N. A. J. M.Sommerdijk, Angew. Chem., Int. Ed., 2002, 41, 4239.

316 A. J. Dirks, S. S. van Berkel, N. S. Hatzakis, J. A. Opsteen,F. L. van Delft, J. J. L. M. Cornelissen, A. E. Rowan,J. C. M. van Hest, F. P. J. T. Rutjes and R. J. M. Nolte,Chem. Commun., 2005, 4172.

317 J. F. Lutz and H. G. Boerner, Prog. Polym. Sci., 2008, 33, 1.318 K. Holmberg, in Reactions and Synthesis in Surfactant

Systems, ed. J. Texter, Dekker, New York, 2001, pp. 45–58.319 Y. Liu, P. G. Jessop, M. Cunningham, C. A. Eckert and

C. L. Liotta, Science, 2006, 313, 958.320 G. I. Peterson, M. B. Larsen and A. J. Boydston, Macro-

molecules, 2012, 45, 7317.321 A. P. J Middelberg, L. He, A. F. Dexter, H.-H. Shen,

S. A. Holt and R. K. Thomas, J. R. Soc., Interface, 2008, 5, 47.322 J. Kim, L. J. Cote, F. Kim, W. Yuan, K. R. Shull and

J. Huang, J. Am. Chem. Soc., 2010, 132, 8180.323 L. J. Cote, J. Kim, Z. Zhang, C. Sun and J. Huang, Soft

Matter, 2010, 6, 6096.324 J. Kim, L. J. Cote and J. Huang, Acc. Chem. Res., 2012,

45, 1356.325 B. J. Kim, G. H. Fredrickson, C. J. Hawker and E. J. Kramer,

Langmuir, 2007, 23, 7804.326 J. Hu, S. Zhou, Y. Sun, X. Fang and L. Wu, Chem. Soc. Rev.,

2012, 41, 4356.

Perspective PCCP

Publ

ishe

d on

05

Apr

il 20

13. D

ownl

oade

d by

Uni

vers

ita d

i Pad

ova

on 2

6/04

/201

6 15

:11:

26.

View Article Online



327 P. Arumugam, H. Xu, S. Srivastava and V. M. Rotello,Polym. Int., 2007, 56, 461.

328 J. Hu, T. Wu, G. Zhang and S. Liu, J. Am. Chem. Soc., 2012,134, 7624.

329 K. Niikura, N. Iyo, T. Higuchi, T. Nishio, H. Jinnai,N. Fujitani and K. Ijiro, J. Am. Chem. Soc., 2012, 134, 7632.

330 X.-C. Yang, B. Samanta, S. S. Agasti, Y. Jeong, Z.-J. Zhu,S. Rana, O. R. Miranda and V. M. Rotello, Angew. Chem.,Int. Ed., 2011, 50, 477.

331 J. Peng, Q. Liu, Z. Xu and J. Masliyah, Adv. Funct. Mater.,2012, 22, 1732.

332 X. Batlle and A. Labarta, J. Phys. D: Appl. Phys., 2002,35, R15.

333 U. Resch-Genger, M. Grabolle, S. Cavaliere-Jaricot,R. Nitschke and T. Nann, Nat. Methods, 2008, 5, 763.

334 S. Eustis and M. A. El-Sayed, Chem. Soc. Rev., 2006, 35, 209.335 B. Wang, B. Li, B. Zhao and C. Y. Li, J. Am. Chem. Soc., 2008,

130, 11594.336 C. Gentilini and L. Pasquato, J. Mater. Chem., 2010, 20, 1403.337 J. Song, L. Cheng, A. Liu, J. Yin, M. Kuang and H. Duan,

J. Am. Chem. Soc., 2011, 133, 10760.338 J. D. Hartgerink, E. Beniash and S. I. Stupp, Science, 2001,

294, 1684.339 Z. Zhang and S. C. Glotzer, Nano Lett., 2004, 4, 1407.340 E. R. Zubarev, J. Xu, A. Sayyad and J. D. Gibson, J. Am.

Chem. Soc., 2006, 128, 15098.341 G. Lu, H. Usta, C. Risko, L. Wang, A. Facchetti,

M. A. Ratner and T. J. Marks, J. Am. Chem. Soc., 2008,130, 7670.

342 R. T. M. Jakobs, J. van Herrikhuyzen, J. C. Gielen, P. C. M.Christianen, S. C. J. Meskers and A. P. H. J. Schenning,J. Mater. Chem., 2008, 18, 3438.

343 J. van Herrikhuyzen, G. Portale, J. C. Gielen, P. C. M.Christianen, N. A. J. M. Sommerdijk, S. C. J. Meskers andA. P. H. J. Schenning, Chem. Commun., 2008, 697.

344 L. Hong, A. Cacciuto, E. Luijten and S. Granick, Langmuir,2008, 24, 621.

345 Y. Wei, K. J. M. Bishop, J. Kim, S. Soh and B. A. Grzybowski,Angew. Chem., Int. Ed., 2009, 48, 9477.

346 K. J. M. Bishop, C. E. Wilmer, S. Soh and B. A. Grzybowski,Small, 2009, 5, 1600.

347 B. Wang, B. Li, B. Dong, B. Zhao and C. Y. Li, Macromole-cules, 2010, 43, 9234.

348 Q. Chen, S. C. Bae and S. Granick, Nature, 2011, 469, 381.349 D. M. Andala, S. H. R. Shin, H.-Y. Lee and K. J. M. Bishop,

ACS Nano, 2012, 6, 1044.350 B. J. Park and D. Lee, Soft Matter, 2012, 8, 7690.351 T. Brugarolas, B. J. Park, M. H. Lee and D. Lee, Adv. Funct.

Mater., 2011, 21, 3924.352 B. J. Park, T. Brugarolas and D. Lee, Soft Matter, 2011,

7, 6413.353 M. M. Telo da Gama and K. E. Gubbins, Mol. Phys., 1986,

59, 227.354 B. Smit, Phys. Rev. A: At., Mol., Opt. Phys., 1988, 37, 3431.355 B. Smit, A. Schlijper, L. Rupert and N. Van Os, J. Phys.

Chem., 1990, 94, 6933.

356 L. Rekvig, M. Kranenburg, B. Hafskjold and B. Smit,Europhys. Lett., 2003, 63, 902.

357 L. Rekvig, M. Kranenburg, J. Vreede, B. Hafskjold andB. Smit, Langmuir, 2003, 19, 8195.

358 S. S. Jang, S. T. Lin, P. K. Maiti, M. Blanco, W. A. GoddardIII, P. Shuler and Y. Tang, J. Phys. Chem. B, 2004,108, 12130.

359 J. Chanda and S. Bandyopadhyay, J. Phys. Chem. B, 2006,110, 23482.

360 W. Shinoda, R. Devane and M. L. Klein, Mol. Simul., 2007,33, 27.

361 W. Shinoda, R. DeVane and M. L. Klein, Soft Matter, 2008,4, 2454.

362 B. D. Marshall, K. R. Cox and W. G. Chapman, Soft Matter,2012, 8, 7415.

363 B. D. Marshall, C. Emborsky, K. Cox and W. G. Chapman,J. Phys. Chem. B, 2012, 116, 2730.

364 B. D. Marshall, K. R. Cox and W. G. Chapman, J. Phys.Chem. C, 2012, 116, 17641.

365 X. B. Zhao, F. Pan, H. Xu, M. Yaseen, H. H. Shan,C. A. E. Hauser, S. G. Zhang and J. R. Lu, Chem. Soc.Rev., 2010, 39, 3480.

366 X. Mulet, D. F. Kennedy, T. L. Greaves, L. J. Waddington,A. Hawley, N. Kirby and C. J. Drummond, J. Phys. Chem.Lett., 2010, 1, 2651.

367 T. L. Greaves, A. Weerawardena and C. J. Drummond, Phys.Chem. Chem. Phys., 2011, 13, 9180.

368 T. L. Greaves, D. F. Kennedy, N. Kirby andC. J. Drummond, Phys. Chem. Chem. Phys., 2011, 13, 13501.

369 Z. Chen, T. L. Greaves, C. Fong, R. A. Caruso andC. J. Drummond, Phys. Chem. Chem. Phys., 2012, 14, 3825.

370 C. Fong, T. Le and C. J. Drummond, Chem. Soc. Rev., 2012,41, 1297.

371 V. Castelletto, G. Cheng, C. Stain, C. J. Connon andI. W. Hamley, Langmuir, 2012, 28, 11599.

372 I. W. Hamley, Soft Matter, 2011, 7, 4122.373 J. B. Matson, R. H. Zha and S. I. Stupp, Curr. Opin. Solid

State Mater. Sci., 2011, 15, 225.374 V. Castelletto, G. Cheng, B. W. Greenl, I. W. Hamley and

P. J. F. Harris, Langmuir, 2011, 27, 2980.375 H.-J. Kim, T. Kim and M. Lee, Acc. Chem. Res., 2011, 44, 72.376 T. Shimizu and M. Masuda, J. Am. Chem. Soc., 1997,

119, 2812.377 K. Liu, Y. Yao, Y. Liu, C. Wang, Z. Li and X. Zhang,

Langmuir, 2012, 28, 10697.378 J. Zhang, X. Li and X. Li, Prog. Polym. Sci., 2012, 37, 1130.379 S. Liu, N. C. Billingham and S. P. Armes, Angew. Chem., Int.

Ed., 2001, 40, 2328.380 R. A. Jones, C. Y. Cheung, F. E. Black, J. K. Zia, P. S. Stayton,

A. S. Hoffman and M. R. Wilson, Biochem. J., 2003, 372, 65.381 C. de las Heras Alarcon, S. Pennadam and C. Alexander,

Chem. Soc. Rev., 2005, 34, 276.382 X. Yin, A. S. Hoffman and P. S. Stayton, Biomacromolecules,

2006, 7, 1381.383 H. Mori, I. Kato and T. Endo, Macromolecules, 2009,

42, 4985.

PCCP Perspective

Publ

ishe

d on

05

Apr

il 20

13. D

ownl

oade

d by

Uni

vers

ita d

i Pad

ova

on 2

6/04

/201

6 15

:11:

26.

View Article Online



384 A. Klaikherd, S. Ghosh and S. Thayumanavan, Macromole-cules, 2007, 40, 8518.

385 D. Roy, J. N. Cambre and B. S. Sumerlin, Prog. Polym. Sci.,2010, 35, 278.

386 A. Salonen, D. Langevin and P. Perrin, Soft Matter, 2010,6, 5308.

387 B. Bharti, M. Xue, J. Meissner, V. Cristiglio and G. H.Findenegg, J. Am. Chem. Soc., 2012, 134, 14756.

388 M. Lotya, Y. Hernandez, P. J. King, R. J. Smith, V. Nicolosi,L. S. Karlsson, F. M. Blighe, S. De, W. Zhiming,I. T. McGovern, G. S. Duesberg and J. N. Coleman, J. Am.Chem. Soc., 2009, 131, 3611.

389 M. Lotya, P. J. King, U. Khan, S. De and J. N. Coleman, ACSNano, 2010, 4, 3155.

390 R. J. Smith, M. Lotya and J. N. Coleman, New J. Phys., 2010,12, 125008.

391 A. Griffith and S. M. Notley, J. Colloid Interface Sci., 2012,369, 210.

392 S. M. Notley, Langmuir, 2012, 28, 14110.393 Y.-J. Guo, J.-X. Liu, X.-M. Zhang, R.-S. Feng, H.-B. Li,

J. Zhang, X. Lv and P.-Y. Luo, Energy Fuels, 2012, 26, 2116.394 J.-X. Liu, Y.-J. Guo, J. Hu, J. Zhang, X. Lv, X.-M. Zhang,

X.-S. Xue and P.-Y. Luo, Energy Fuels, 2012, 26, 2858.395 H. Zhang, M. Dong and S. Zhao, Energy Fuels, 2010,

24, 1829.

396 D. Nguyen, N. Sadeghi and C. Houston, Energy Fuels, 2012,26, 2742.

397 M. Mulqueen and D. Blankschtein, Langmuir, 2002,18, 365.

398 Y. Cao, R.-H. Zhao, L. Zhang, Z.-C. Xu, Z.-Q. Jin, L. Luo,L. Zhang and S. Zhao, Energy Fuels, 2012, 26, 2175.

399 M. Meister, J. J. Amsden, I. A. Howard, I. Park, C. Lee,D. Y. Yoon and F. Laquai, J. Phys. Chem. Lett., 2012, 3, 2665.

400 J. Carlstedt, D. Lundberg, R. S. Dias and B. Lindman,Langmuir, 2012, 28, 7976.

401 E. Grueso, C. Cerrillos, J. Hidalgo and P. Lopez-Cornejo,Langmuir, 2012, 28, 10968.

402 K. M. Wasan, D. R. Brocks, S. D. Lee, K. Sachs-Barrable andS. J. Thornton, Nat. Rev. Drug Discovery, 2008, 7, 84.

403 K. M. Wasan and J. S. Conklin, Clin. Infect. Dis., 1997,24, 78.

404 R. Tory, K. Sachs-Barrable, C.-B. Goshko, J. S. Hill andK. M. Wasan, Transplantation, 2009, 88, 62.

405 G. A. A. Saracino, D. Cigognini, D. Silva, A. Caprini andF. Gelain, Chem. Soc. Rev., 2013, 42, 225.

406 W. Zheng, W. Zhang and X. Jiang, Adv. Healthcare Mater.,2013, 2, 95.

407 D. Gode and D. A. Volmer, Analyst, 2013, 138, 1289.408 M. Beneito-Cambra, J. M. Herrero-Martinez and

G. Ramis-Ramos, Anal. Methods, 2013, 5, 341.

Perspective PCCP

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