Journal of Structural Biology 126, 179–181 (1999)Article ID jsbi.1999.4131, available online at http://www.idealibrary.com on

EDITORIAL

Biomineralization: Structural Questionsat All Length Scales

The field of biomineralization covers all phenomena that involve mineralformation by organisms. This includes the string of 50-nm-long magnetitecrystals formed intracellularly by some bacteria, the two crystal spicularskeleton of the larvae of sea urchins, and the huge molars and bones ofelephants. The products of biomineralization thus span length scales fromnanometers to meters. Their functions are almost as varied: sound reception,gravity perception, toxic waste disposal, orientation in the earth’s magneticfield, temporary storage of ions, and a diverse array of materials that arestiffened and hardened by the presence of mineral. Bones, teeth, and shells ofall kinds are often the ‘‘major business’’ of this community. The materials usedinclude more than 60 different mineral types, an array of structural proteinsand polysaccharides, and many dedicated glycoproteins, whose major functionsare to control in one way or another the mineralization process.

The inherent order of many of the tissues that contain biologically producedminerals makes this field a veritable treasure trove for problems in structuralbiology. They, like almost all problems in structural biology, generally addressthe core issues of structure–function relations. This special issue on biomineral-ization contains seven reviews of very different subjects within the field thatreflect the diversity of the area, some current state-of-the-art issues, and theheavy dependence on structural methodologies of all kinds.

The most basic processes in biomineralization operate at the nanometerlength scales and involve proteins and/or other macromolecules directly incontrolling the nucleation, growth, and inhibition of the mineral phase. One ofthe best studied examples of problems of this type is ferritin, which is anunusual protein involved with the storage and transport of iron (Chasteen andHarrison). Ferritin is self-assembled from 24 polypeptide subunits to produce aporous hollow shell that acts as a nanostructured cage for the deposition ofsmall particles of iron oxide. By studying the relationships between proteinstructure and function, Chasteen and Harrison highlight how mineralizationreactions can be regulated in confined architectures by a combination of kineticprocesses involving ferrioxidase activity and ion clustering.

Whereas the mineral core of ferritin has no specific shape—usually theparticles are irregular or spherical—the calcium carbonate crystals formedwithin the intracellular vesicles of certain marine algae have striking morpho-logical form (Young et al.). The complexity of these structures (coccoliths) isbreath-taking and is a testament to the sophistication of biomineralizationprocesses in single-celled organisms. Although more information on theinorganic crystallography of coccoliths is coming to light, little progress hasbeen made on the molecular and macromolecular structures that are associatedwith these biominerals. Many questions remain to be answered: How can suchelaborate inorganic forms be sculptured by soft biological structures andsystems? And what role does structural biology play in the evolution ofinorganic morphogenesis?

For more than a century, the sea urchin larva has been the focus of studies of

all types and today is still one of the best characterized systems in developmen-

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tal biology. Since the mid-eighties, several research groups have studied theformation of the two spicules that constitute the skeleton of the larva. Today weknow that tens of different proteins are occluded within the spicule. We alsoknow much about several of these proteins, as well as the mineral phasesthemselves. In fact, this body of information may well represent the state-of-the-art in the field of biomineralization, in terms of the characterization of theproteins that are in intimate association with the mineral phase (Wilt).

Shells are commonplace biominerals usually made from a composite struc-ture of calcium carbonate in a matrix of protein and polysaccharide. The shellsof one group within the brachiopod phylum, however, consist of calciumphosphate in the form of carbonated apatite and therefore represent a distinctphylogeny that can be traced for hundreds of millions of years through the fossilrecord (Williams and Cusack). The textures and fabrics of these structures areas complex as those of any of the calcium carbonate shells, and information onmineral-associated biomolecules is becoming available. One teasing question iswhether any of the mineralization mechanisms operating in these inverte-brates are precursors or even analogs to the large-scale structures of vertebratemineralization, which not surprisingly are the most actively investigated of allbiominerals.

The vertebrates, as their very name suggests, are sophisticated skeletonformers. In fact, bone is really a family of materials in which the basic buildingblock is the mineralized collagen fibril. The manner in which the fibrils areorganized varies in different tissues, and the main variants, such as lamellar orparallel fibered bone, dentin, or calcified tendon, constitute the members of thefamily. This diversity presents many fascinating opportunities for relatingstructure to function. The lamellar bone structure is perhaps the most complex.It is also the most common form in humans. Relating its structure to themechanical functions it performs is a challenge indeed (Weiner, Traub, andWagner). The formation processes themselves involve many different proteins.Unfortunately, we know very little about the functions of any of these proteins.One of the most powerful tools we have for discerning function in tissues of thistype is to identify the location of a protein within the matrix framework(Nanci). The working surfaces of vertebrate teeth (enamel) are highly special-ized mineralized structures that are exquisitely structured for performing acrucial function—mastication. The mode of formation of enamel is highlyunusual, as it involves the building up of the tissue in a proteinaceousframework and then the breaking down of this framework for further crystalgrowth to achieve the required hardness (Fincham, Moradian-Oldak, andSimmer).

Finally, we draw attention to the important applications of biomineralizationand the need for increased activity among structural biologists in this field.Clearly, biomineralized tissues such as bones and teeth continue to be offundamental importance in medicine and health care. Monitoring the struc-tural integrity and dynamics of these materials requires high-resolutionreal-time analysis of complex multifunctional composites. Moreover, for predict-ing and understanding the mechanical properties of many biominerals, newtools and methods are required to determine the molecular nature of theboundaries between the mineral and organic matrix components. The struc-tural biology of heterogeneous interfaces needs to be developed!

Further afield, there are important implications of biomineralization re-search for new advances in materials science. For example, there is a growingarea of interest in the use of biomineralization proteins and their syntheticanalogues for the control of crystal properties and organization. It is very likelythat biomolecules will be used as templates for the fabrication of inorganicsystems such as electronic devices, new catalysts, sensors, and porous materi-

als, as well as biomimetic structures for more conventional uses in biomaterials

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engineering. In each case, knowledge of the underlying biological structures isthe basis for all novel applications.

Steve MannSchool of ChemistryUniversity of BristolBristol BS8 1TS, United Kingdom

Steve WeinerDepartment of Structural BiologyWeizmann Institute of ScienceRehovot, Israel 76100