biopolymers structure and properties.pptx

7/28/2019 Biopolymers structure and properties.pptx

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Biopolymers structure and

properties



Biopolymers/Natural polymers

Definition: Natural polymers are formed in natureduring the growth cycles of all organisms, hence theyare also referred to as biopolymers.

Their synthesis generally involves enzyme-catalyzed,chain growth polymerization reactions of activated

monomers, which are formed typically within cells bycomplex metallic processes



Types

• Polysaccharide based polymers

– Starch, Cellulose in higher plants, Chitin/Chitosan

• Protein based polymers

– Protein collagen in animals, Gelatin, Silk Proteins,Albumin etc.

• Microbial polyesters

– Poly--hydroxyalkanoates



Collagen

• Types of collagen

• Structure of collagen

• Biosynthesis of

collagen



• Collagen is the most abundant fibrousprotein, which occur in vertebrates.

• A typical collagen molecule is a long, rigid

structure in which three polypeptides "-

chains" are wound around one another in a

rope-like triple-helix

COLLAGEN



• Although collagen molecules are found

throughout the body, their types andorganization are dictated by the structural

role collagen plays in a particular organ.

• In some tissues, collagen may be dispersed as

a gel support to the structure, as in the

extracellular matrix or the vitreous humor of the eye.



• In other tissues, collagen may be bundled intight, parallel fibers great strength, as in

tendons.

• In the cornea of the eye, collagen is stacked transmit light with a minimum of scattering.

• Collagen of bone occurs as fibers arranged at anangle to each other resist mechanical shear

from any direction.



A. Types of collagen

• The collagen superfamily of proteins includes

more than 20 collagen types, and proteins

that have collagen-like domains.

• The three polypeptide -chains are held

together by hydrogen bonds between the

chains.



• Variations in the amino acid sequence of the

-chains structural components that areabout the same size (approximately 1000

amino acids long), but with slightly different

properties.

• These -chains are combined to form the

various types of collagen found in the tissues.



1. Fibril-forming collagens:

•

Types I, II, and Ill are the fibrillar collagens,and have the rope-like structure describedbefore for a typical collagen molecule.

• In the electron microscope, these linearpolymers of fibrils have characteristicbanding patterns reflecting the regular

staggered packing of the individual collagenmolecules in the fibril(Figure 4.3).



• Type I collagen fibers are found in supportingelements of high tensile strength (e.g. tendonand cornea).

• Fibers formed from type II collagen molecules

are restricted to cartilaginous structures.

• Fibrils derived from type Ill collagen are

prevalent in more distensible tissues, such asblood vessels.



2. Network-forming collagens:

•

Types IV and VII form a three-dimensional mesh,rather than distinct fibrils (Figure 4.4).

• For example, type IV molecules assemble into a sheet

or meshwork that constitutes a major part of basement membranes.

• [ Basement membranes are thin, sheet-like structures

that provide mechanical support for adjacent cells, and function as a semipermeable filtration barrier for

macromolecules in organs such as the kidney and the

lung.]



3. Fibril-associated collagens:

• Types IX and XII bind to

the surface of collagen

fibrils, linking these

fibrils to one another

and to other

components in the

extracellular matrix(Figure 4.2).



B. Structure of collagen

1. Amino acid sequence: • Collagen is rich in proline and glycine, both of

which are important in the formation of the

triple-stranded helix.

• Proline facilitates the formation of the

helical conformation of each -chain becauseits ring structure "kinks" in the peptide

chain.



glycine

proline

oxygennitrogen

carbon



• Glycine, the smallest amino acid, is found in

every third position of the polypeptide chain.

• It fits into the restricted spaces where the

three chains of the helix come together.



• The glycine residues are part of a repeating

sequence.—

Gly—

X—

Y—

, where X isfrequently proline and Y is often hydroxyproline

or hydroxylysine (Figure 4.5).

• Most of the .- chain can be regarded as a

polytripeptide whose sequence can be

represented as (—

Gly—

X—

Y—

) 333



2. Triple-helical structure: • Unlike most globular proteins that are folded into

compact structures, collagen, a fibrous protein, has

an elongated, triple-helical structure that places

many of its amino acid side chains on the surface of

the triple-helical molecule.

• [This allows bond formation between the exposed

R-groups of neighboring collagen monomers

aggregation into long fibers]



3. Hydroxyproline and hydroxylysine:

• Collagen contains hydroxyproline (hyp) and

hydroxylysine (hyl), which are not present in

most other proteins.

• These residues result from the hydroxylation

of some of the proline and lysine residues

after their incorporation into polypeptide

chains

(Figure 4.6).



•

The hydroxylation is, thus, an example of posttranslational modification .

•

Hydroxyproline is important in stabilizing thetriple-helical structure of collagen because it

maximizes interchain hydrogen bond

formation.



4. Glycosylation:

• The hydroxyl group of the hydroxylysineresidues of collagen may be enzymatically

glycosylated.

• Most commonly, glucose and galactose are

sequentially attached to the polypeptide

chain prior to triple-helix formation(Figure 4.7).



C. Biosynthesis of collagen

•

The polypeptide precursors of the collagenmolecule are formed in fibroblasts (or in the

related osteoblasts of bone and chondroblasts

of cartilage), and are secreted into the

extracellular matrix.

• After enzymic modification, the mature collagen

monomers aggregate and become cross-linked collagen fibrils.



1. Formation of pro- -chains:

– Collagen is one of many proteins that normally

function outside of cells.

– Like most proteins produced for export, the

newly synthesized polypeptide precursors of -

chains contain a special amino acid sequence at

their N-terminal ends.

–

This acts as a signal that the polypeptide beingsynthesized is destined to leave the cell.



– The signal sequence:

• facilitates the binding of ribosomes to therough endoplasmic reticulum (RER)

• directs the passage of the polypeptide

chain into the cisternae of the RER.• is rapidly cleaved in the endoplasmic

reticulum precursor of collagen called a

pro--chain (Figure 4.7).



2. Hydroxylation:

• The pro- -chains are processed by a number

of enzymic steps within the lumen of the RER

while the polypeptides are still being

synthesized (Figure 4.7).

• Proline and lysine residues found in the Y-

position of the—Gly—X—Y— sequence can

be hydroxylated hydroxyproline and

hydroxylysine residues.



• These hydroxylationreactions require

molecular oxygen andthe reducing agentvitamin C

•

the hydroxylatingenzymes, prolyl hydroxylase and lysyl hydroxylase, are unable

to function without vit. C(Figure 4.6).



• In the case of vit.C deficiency (therefore, a lack of

prolyl and lysyl hydroxylation), collagen fibers

cannot be cross-linked, greatly

the tensilestrength of the assembled fiber.

• Vit.C deficiency disease known as scurvy.

• Patients with vit.C deficiency often show bruises on

the limbs as a result of subcutaneous extravasation

of blood (capillary fragility) ( Figure 4.8)



3. Glycosylation:

• Some hydroxylysine residues are modified by

glycosylation with glucose or glucosyl-

galactose (Figure 4.7).



4. Assembly and secretion:

• After hydroxylation and glycosylation, pro--

chains form procollagen , a

precursor of collagen that has a central

region of triple helix flanked by the non-helical amino- and carboxyl-terminal

extensions called propeptides.

(Figure 4.7).



• The formation of procollagen begins with

formation of interchain disulfide bondsbetween the C-terminal extensions of the

pro-- chains.

• This brings the three -chains into an

alignment favorable for helix formation.



• The procollagen molecules are translocated

to the Golgi apparatus, where they arepackaged in secretory vesicles.

• The vesicles fuse with the cell membrane release of procollagen molecules into the

extracellular space.



5. Extracellular cleavage of procollagen

molecules:

• After their release, the procollagen

molecules are cleaved by N - and C –

pro -collagen peptidases remove the terminal

propeptides releasing triple-helical

collagen molecules.

6 F i f ll fib il



6. Formation of collagen fibrils:

• Individual collagen molecules spontaneously

associate form fibrils.

• They form an ordered, overlap ping, parallel

array, with adjacent collagen moleculesarranged in a staggered pattern.

• Each collagen molecule overlaps its neighbor

by three-quarters of its length.

(Figure 4.7).



7. Cross-link formation:

• The fibrillar array of collagen molecules

serves as a substrate for lysyl oxidase.

• This extracellular enzyme oxidatively

deaminates some of the lysyl and

hydroxylysyl residues in collagen.



• The reactive aldehydes that result (allysine and

hydroxyallysine) condense with lysyl or

hydroxylysyl residues in neighboring collagenmolecules form covalent cross-links (Figure

4.9).

•

This cross-linking is essential for achieving the tensilestrength necessary for the proper functioning of

connective tissue.

• Any mutation that interferes with the ability of

collagen to form cross-linked fibrils affects thestability of the collagen].



Contribution of Collagen

The major fraction of connective tissue iscollagen

• This component is important because it

contributes significantly to toughness inmammalian muscle

• Gelatin serves as the functional ingredient in

temperature—Dependent Gel-type desserts



Solubility

• Some of the collagen is soluble in neutral saltsolution

• Some in soluble in acid

• Some is insoluble



The collagen triple helix

A case of structure following composition

• The unusual amino acid composition of collagen isunsuited for alpha helices or beta sheets

• But it is ideally suited for the collagen triple helix; threeintertwined helical strands

• Much more extended than alpha helix, with a rise perresidue of 2.9 Angstroms

•

3.3residues per turn• Long stretches of Gly-Pro-Pro/Hyp



The Fabric of Collagen

• The collagen monomer is a long cylindricalprotein about 2800 Å long and 14-15 Å indiameter

• It consists of three poly peptide chains woundaround each other in a suprahetical fashion



Collagen degradation

• Collagen can be degraded by the enzymecalled collagenase.

• Activity of collagenase will be reduced if

collagen is crosslinked with metal ions whichact as a enzyme poisons.

• Gelatin is the byproduct of collagen

degradation by acid or alkaline digestion



Stability of collagen

• Affected by dehydration – Contact with reagents which reduce hydrophobic

interaction

– Heat – Mucopolysaccharides



Contents:

•

Elastin – Structure of elastin



ELASTIN

• In contrast to collagen, which forms fibers

that are tough and have high tensile

strength, Elastin is a connective tissueprotein with rubber-like properties.



• Elastic fibers composed of elastin and

glycoprotein microfibrils are found in the

lungs, the walls of large arteries, and elastic

ligaments.

• They can be stretched to several times their

normal length, but recoil to their original

shape when the stretching force is relaxed.



A. Structure of elastin

• Elastin is

– an insoluble protein polymer

– synthesized from a precursor,

tropoelastin , ( a linear polypeptide composed of about 700 amino acids that are primarily

small and nonpolar) (e.g. glycine,

alanine, and valine).

• Elastin is also,



Elastin is also,

– rich in proline and lysine,

– contains a little hydroxyproline

– contains no hydroxylysine.

• Tropoelastin is secreted by the cell into theextracellular space.

• There, it interacts with specific glycoproteinmicrofibrils, such as fibrillin, which function as ascaffold onto which tropoelastin is deposited.

• Some of the lysyl side chains of the tropoelastin



Some of the lysyl side chains of the tropoelastin

polypeptides are oxidatively deaminated by lysyl

oxidase forming allysine residues.

• 3 of the allysyl side chains + one unaltered lysyl

side chain from the same or neighboring

polypeptides form a desmosine cross-link.

(Figure 4.12).

This produces Elastin - an extensively

interconnected, rubbery network that can stretch

and bend in any direction when stressed

connective tissue elasticity

(Figure 4.13).



Elastin is stable to relatively high temperaturesand chemical reagents due to low content of aminoacids with polar side chains. The enzyme elastase,hydrolyses elastin at peptide bonds after small

hydrophobic residues, particluarly alanine.

Mechanical properties of elastin and



Mechanical properties of elastin andcollagen fibers

Fibers Modulus of

elasticity

Mpa

Tensile

strength

Mpa

Ultimate

elongation %

Elastic fibers 0.6 1 100

Collagenfibers

1000 50-1000 10



61

mechanics of BIO materials



Extracellular Macromolecules

1. GlycosaminoglycansProteoglycans

GlycoproteinsMucins



Extracellular Macromoleculesmacromolecule % carb.

glycosaminoglycans* (GAGs) 100

proteoglycans* 90-95

glycoproteins 2-30

fibrous proteins 1-2

Examples of functions:

mechanical support lubrication

cushioning adhesivescell spacers selective filters

* aka mucopolysaccharides, mucoproteins, respectively 1

Extracellular matrix in tissues



Extracellular matrix in tissues

• ground substance + fibers

• macromolecules between cells – ground substance molecules

GAGs/proteoglycans (mostly carbohydrate)

– fibersfibrous proteins:

structuraladhesive

• especially abundantin connective tissue

adhesionmolecules

Adapted from Hypercell

extra-cellularmatrix

basallamina

underlying cells

epithelial cells

2

GAG structure OO – A sugar



GAG structure

• exist as: –

independent moleculese.g., hyaluronate & heparin –parts of larger structures

e.g., in proteoglycans

•

heteropolysaccharidesrepeating structure:disaccharide ( AB)n ABABAB…

– where A is usually 1 uronic acid (hexose with C6 as COO – )

– & B is 1 glycosamine (amino sugar) derivative

• unbranched –glycosidic linkage –anomeric C of 1 unit linked to hydroxyl of adjacent unit

OHO

OHOH

C

OH

OHOH

O

OH

CH2

NH2

g

B sugar

3

GAG structure: repeating units 4



GAG structure: repeating unitsGAG A sugar B sugar

hyaluronate glucuronate N-acetyl glucosamine

OO

OH OH

COO

OOH

O

O

CH2 OH

CH3 O

NH1,3

1,4

–

25*

GAG structure: repeating units

4



GAG structure: repeating unitsGAG A sugar B sugar

hyaluronate glucuronate N-acetyl glucosamine

chondroitin sulfate glucuronate N-Ac galactosamine 4-SO4

dermatan sulfate iduronate "

heparan sulfate glucuronate glucosamine N-SO3, 6-SO4

heparin iduronate 2-SO4 "

keratan sulfate galactose N-Ac glucosamine 6-SO4

*opposite configuration in iduronateglucuronate/iduronate: epimers at C5 glucose/galactose: epimers at C4

OO

OH OH

COO

OOH

O

O

CH2 OH

CH3 O

NH1,3

1,4

–

25*



9.5 Proteoglycans

• Example: syndecan - transmembrane protein -inside domain interacts with cytoskeleton,outside domain interacts with fibronectin

Hyaluronate (aka hyaluronan)

5



Hyaluronate (aka hyaluronan)• mol wt: 106 – 107 (5000 – 50,000 monosaccharide

units)

• very polar: 2 hydroxyls/unit 6 heteroatoms/unitCOO – every other unit

binds cations: Na+, Ca++

2 1 3 4 5 6

–

– –

(glucuronate –N-acetyl glucosamine)3 (glcUA –glcNAc)3

A B A B A B

Display of HAin motion

http://localhost/var/www/apps/conversion/tmp/scratch_3//SFDATA1/DATA2/USER/AMURPHY/PRESNTTN/S11L01/ChimeScrpt/Hyastick.htm







Proteoglycan Functions

• Modulation of cell growth processes

– Binding of growth factor proteins by proteoglycansin the glycocalyx provides a reservoir of growthfactors at the cell surface

• Cushioning in joints

– Cartilage matrix proteoglycans absorb large

amounts of water. During joint movement, cartilageis compressed, expelling water!



Proteoglycans (PGs)



g y ( )• composed of as many as 200 GAG chains covalently bonded to a core protein via

serine side chains• molecular weight range: 105 – 107 • GAG chains: chondroitin sulfate, heparan sulfate,

dermatan sulfate, keratan sulfateExamples• decorin

– many connective tissues – binds type I collagen, TGF-

• perlecan – basal laminae – structural & filtering function

• aggrecan• syndecan (slide 13)

from Alberts et al.

Fig. 19-57

GAG chains

coreprotein

AlbertsT 19-3:Dcrn GAGchndSO4

/drmSO4

9

Proteoglycans: aggrecan



oteog yca s: agg eca

• ~100 GAG chains/molecule

• ~100 monosaccharides/GAG chain• each "bristle" = 1 GAG chain

• each GAG chain is either chondroitin sulfate

or keratan sulfate• GAG chains linked to ser side chains of core protein

coreprotein

GAG chains11

An aggregate of aggrecans & hyaluronanj GAG PG 1m



gg g gg y• major GAG –PG

in cartilage

• link proteins bindnoncovalently

• with bound H2O,disperses shocks,compressive force

• ~ cell size• adhesion proteins

link to collagen &cells

• degraded bychondroitinsulfatase, etc

1m

hyalur-

onan

link proteins

keratansulfate chondroitin

sulfate

Alberts et al. Fig. 19-41

core protein

12

Proteoglycans:d



g ysyndecan

GAG chains

core

• cell-surface PG• core protein domains

–intracellular –transmembrane –

extracellular5 GAGs attached

• functions –interactions

• cell-cell• cell-matrix

–growth factor receptor

outside

inside

biopolymers structure and properties.pptx

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