Assembly of elastin

Coacervation occurs in tropoelastin solutions and is a precursor event in the assembly of elastin nanofibrils [42]. This phenomenon is thought to be mainly due to the interaction between hydro-phobic domains of tropoelastin. In scanning electron microscopy (SEM) picmres, nanofibril stmc-tures are visible in coacervate solutions of elastin-based peptides [37,43]. Indeed, Wright et al. [44] describe the self-association characteristics of multidomain proteins containing near-identical peptide repeat motifs. They suggest that this form of self-assembly occurs via specific intermolecular association, based on the repetition of identical or near-identical amino acid sequences. This specificity is consistent with the principle that ordered molecular assembhes are usually more stable than disordered ones, and with the idea that native-like interactions may be generally more favorable than nonnative ones in protein aggregates. 

Miao, M., Cimlis, J.T., Lee, S., and Keeley, F.W., Stmctural determinants of cross-hnking and hydro-phobic domains for self-assembly of elastin-hke pol3fpeptides. Biochemistry, 44(43), 14367-14375, 2005. 

Keeley, F.W., Bellingham, C.M., and Woodhouse, K.A., Elastin as a self-organising biomaterial Use of recombinantly expressed human elastin polypeptides as a model system for investigations of structure and self-assembly of elastin, Philos. Trans. R. Soc. Lond. B Biol. Sci., 357, 185-189, 2002. 

Miao M, Cirulis JT, Lee S et al (2005) Structural determinants of cross- linking and hydrophobic domains for self-assembly of elastin-like polypeptides. Biochemistry 44 14367-14375... 

Yang G, Woodhouse KA, Yip CM. Substrate-facilitated assembly of elastin-like peptides studies by variable-temperature in situ atomic force microscopy. J. Am. Chem. Soc.,... 

Hybrid Nanofibres via Self-Assembly of Elastin-Like Polymers Templating Cadmium... 

Wright E.R., McMillan R., Andrew C.A., Apkarian, R.P., and Conticello, V.P. Thermoplastic elastomer hydrogels via self-assembly of an elastin-mimetic triblock polypeptide, Adv. Func. Mater., 12, 149, 2002. 

Lee T.A.T., Cooper A., Apkarian R.P., and Conticello V.P. Thermo-reversible self-assembly of nano-particles derived from elastin-mimetic polypeptides. Advanced Materials, 12, 1105, 2000. 

This coacervation process forms the basis for the self-assembly, which takes place prior to the crosslinking. The assembly of tropoelastin is based on an ordering process, in which the polypeptides are converted from a state with little order to a more structured conformation [8]. The insoluble elastic fiber is formed via the enzymatic crosslinking of tropoelastin (described in Sect. 2.1). Various models have been proposed to explain the mechanism of elasticity of the elastin fibers. 

In developing elastic tissue, the microfibrils are the first components to appear in the extracellular matrix. They are then thought to act as a scaffold for deposition, orientation, and assembly of tropoelastin monomers. They are 10—12 nm in diameter, and lie adjacent to cells producing elastin and parallel to the long axis of the developing elastin fiber (Cleary, 1987). 

Mithieux, S. M., Rasko, J. E., and Weiss, A. S. (2004). Synthetic elastin hydrogels derived from massive elastic assemblies of self-organized human protein monomers. Biomaterials 25, 4921-4927. 

In Nature, there are many examples of protein and peptide molecular self-assembly. Of the genetically engineered fibrous proteins, collagen, spider silks, and elastin have received attention due to their mechanical and biological properties which can be used for biomaterials and tissue engineering. 

This review focuses upon the post-translational modification and chemical changes that occur in elastin. Outlined are the steps currently recognized as important in the assembly of pro-fibrillar elastin subunits into mature fibers. Descriptions of some of the proposed mechanisms that appear important to the process are also presented. It will be emphasized that from the standpoint of protein deterioration, elastin is a very novel protein. Under normal circumstances, the final product of elastin metabolism, the elastin fiber does not undergo degradation that is easily measured. Unlike the metabolism of many other proteins, deterioration or degradation is most evident biochemically in the initial stages of synthesis rather than as a consequence of maturation. Since the presence of crosslinks is an essential component of mature elastin, a section of this review also addresses important features of crosslink formation. 

Figure 2. Synthesis of mature elastin fibers. Some evidence suggests the possibility for proforms to elastin that appear as the first products of translation. These products are cleaved to tropoelastin (27), which appears to combine with microfibrillar protein. Although post-translational events important to the synthesis of the microfibrillar protein have not been defined, it is clear that it is a major component on which is organized or assembled the profibrillar forms of elastin. Cross-linking is catalyzed by lysyl oxidase, a copper-requiring protein (30). Recent information on the elastin proteinase(s) involved in tropoelastolysis would suggest that proteolysis may also play a role in elastin fiber...

Fibrillin-2 has an amino acid sequence that is 68% identical to fibrillin-1 and is coexpressed with fibrillin-1 in many tissues early in mammalian development. It forms head-to-tail fibrillinl/2 alternating heterodimers that resemble fibrillin-1 homodimers shown at the top of Fig. 6.3. During mammalian development, some tissues express fibrillin-2 without fibrillin-1 and fibrillin-2 homodimers may assemble by a mechanism that does not involve fibrillin-1 but perhaps utilizing fibrillin-3, a third member of the fibrillin family. Fibrillin-2 binds to the precursor of elastin during development and forms stronger elastic fibers than fibrillin-1. Fibrillin-3 is a minor component whose functions are uncertain. 

Conticello and colleagues have studied the potential of amphiphilic diblock (AB) and triblock (ABA) elastin-like copolymers, where A is a hydrophilic and B a hydrophobic block, to reversibly self-assemble into well-defined micellar aggregates (20,30). Collapse of the hydrophobic block above Tt results in the formation of elastin-based nanoparticles. To provide diversity in the mechanical properties of the micellar structures, the amino acid sequence of the hydrophobic block was varied between plastic (VPAVG) and elastomeric (VPGVG) in nature. The hydrophilic block is designed to maintain solubility and form a protective core that prevents protein adsorption and clearance by the reticuloendothelial system. 

Wright ER, Conticello VP. Self-assembly of block copolymers derived from elastin-mimetic polypeptide sequences. Adv Drug Delivery Rev 2002 54 1057-1073. 

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