Elastin biomaterials in dermal repair. Sci. doi: 10.1002/chem.200305661. The liquid structure of elastin. Cardiovasc. Coacervation involves the agglomeration of protein molecules, which is an . Tropoelastin spherules assemble at the cell surface before deposition onto the microfibrillar scaffold in cell culture systems at physiological temperature (Kozel et al., 2006). Engineering a highly elastic human protein-based sealant for surgical applications. The evolutionary background and functional consequences of the rs2071307 polymorphism in human tropoelastin. 26, 17001709. A., Ishibashi, H., Werneck, C. C., Keeley, F. W., Zhang, L., et al. J. Biol. Tropoelastin is a spring-like molecule that is extremely extensible prior to cross-linking. Aaron, B., and Gosline, J. We are very interested in the blend of biochemistry and cell biology, as well as the tissue engineering and regenerative medicine opportunities provided by this amazing elastic protein. (2003). Perturbation of either of these components greatly reduces tropoelastins ability to self-assemble in vitro and interact with the microfibril scaffold of elastic fibers (Nonaka et al., 2014), indicating that an intact domain 36 is required for correct assembly. The elastin receptor complex transduces signals through the catalytic activity of its Neu-1 subunit. doi: 10.1002/bip.23007, Miao, M., Stahl, R. J., Petersen, L. F., Reintsch, W. E., Davis, E. C., and Keeley, F. W. (2009). The understanding of tropoelastins structure has been hindered by numerous intrinsic properties of the molecule. doi: 10.1203/00006450-199010000-00015, Nonaka, R., Sato, F., and Wachi, H. (2014). "We believe it's in the best strategic interest of the company to make this move, which supports Caterpillar's strategy for profitable . doi: 10.1073/pnas.1111615108, Yeo, G. C., Baldock, C., Wise, S. G., and Weiss, A. S. (2017). Evidence for the presence of alpha-aminoadipic acid delta-semialdehyde and its aldol condensation product. Pepe, A., Flamia, R., Guerra, D., Quaglino, D., Bochicchio, B., Pasquali Ronchetti, I., et al. Elastic fibers are eventually formed after extensive cross-linking through a process termed maturation (Yeo et al., 2016). Polymorphisms in the human tropoelastin gene modify in vitro self-assembly and mechanical properties of elastin-like polypeptides. U.S.A. 84, 56805684. doi: 10.1002/jcp.20546, Kozel, B. Matrix Biol. doi: 10.1016/j.ajhg.2009.09.013. In order to eliminate this limitation, human tropoelastin has been expressed in a recombinant bacterial system and the protein has been highly purified. Exp. Sci. While tropoelastin is a flexible molecule, a combination of optical and structural analyses has defined key regions of the molecule that directly contribute to the elastomeric properties and control the cell interactions of the protein. A., Wachi, H., Davis, E. C., and Mecham, R. P. (2003). Biol. Dyn. The reduction in solvent accessible surface area of the mutant molecules suggests that the underlying mechanism for their altered self-assembly properties observed in experiments is due to less exposure of the appropriate hydrophobic domains required for coacervation. Coacervation of tropoelastin. doi: 10.1073/pnas.1801205115, Tarakanova, A., Yeo, G. C., Baldock, C., Weiss, A. S., and Buehler, M. J. All authors contributed to writing and editing the review. Cytochem. The Wellcome Trust Centre for Cell-Matrix Research is supported by funding from Wellcome Trust (203128/Z/16/Z). ACS Biomater. doi: 10.1016/j.str.2006.09.008, Rauscher, S., and Pomes, R. (2017). doi: 10.1016/0014-4800(65)90015-8, He, D., Chung, M., Chan, E., Alleyne, T., Ha, K. C. H., Miao, M., et al. U.S.A. 110, 28522857. doi: 10.1080/07391102.1992.10508661, Tamburro, A. M., Pepe, A., and Bochicchio, B. Cryo-electron microscopy is a rapidly developing method and likely to contribute to structural knowledge of tropoelastin. doi: 10.1016/j.matbio.2007.05.005, He, D., Miao, M., Sitarz, E. E., Muiznieks, L. D., Reichheld, S., Stahl, R. J., et al. Collapse Section. J. Biol. 58, 270277. Acad. 270, 1777817783. Unsubstituted models are also critical to understanding self-assembly. Detailed Description: B., Broekelmann, T. J., et al. Chem. The Weiss Lab's research focuses on the use of human tropoelastin in tissue assembly and wound repair. 28, 432441. Due to the lack of a full-atomistic structure, a number of elastin derivatives, including isolated tropoelastin domains (Toonkool et al., 2001; Mackay et al., 2005; Dyksterhuis et al., 2007; Dyksterhuis and Weiss, 2010) and synthetic elastin-derived peptides (EDPs) (Luan et al., 1990; Tamburro et al., 1992; Kentsis and Sosnick, 1998; Kumashiro et al., 2006; Reichheld et al., 2014, 2017; Muiznieks et al., 2015; MacEwan et al., 2017; Tarakanova et al., 2017) have been studied to understand tropoelastins domain level properties. Int. Overview of the computational and experimental methodologies that have recently contributed to our understanding of elastic fiber assembly. doi: 10.1021/acs.biomac.0c00546, Bochicchio, B., Floquet, N., Pepe, A., Alix, A. J., and Tamburro, A. M. (2004). The cross-linking domains are enriched for either Lys-Pro (KP) or Lys-Ala (KA) motifs and form cross-links that link growing tropoelastin chains during elastogenesis; note that exon 6 encodes a KA domain. Visconti, R. P., Barth, J. L., Keeley, F. W., and Little, C. D. (2003). doi: 10.1074/jbc.M609505200, Dyksterhuis, L. B., Baldock, C., Lammie, D., Wess, T. J., and Weiss, A. S. (2007). Domains in tropoelastin that mediate elastin deposition in vitro and in vivo. Biomacromolecules 18, 599609. Fed. doi: 10.1016/j.matbio.2019.06.010, Reichheld, S. E., Muiznieks, L. D., Stahl, R., Simonetti, K., Sharpe, S., and Keeley, F. W. (2014). Bonnans, C., Chou, J., and Werb, Z. Delineation of unusual features in the 5-flanking region. Interestingly, the location and orientation of different domains that contacted each other during self-assembly was noted to be heterogeneous, resulting in head-to-head, tail-to-tail, head-to-tail, and lateral interactions (Tarakanova et al., 2019a). All rights reserved. doi: 10.1016/j.jmb.2020.08.023, Luan, C. H., Harris, R., Prasad, K. U., and Urry, D. W. (1990). Multimers may undergo further transitions, such as branching, to form spherules made of multimer aggregates (Tu et al., 2010). Specific instructions are found in the Directions for Use. 293, 1510715119. Biochemistry 52, 77317741. Tropoelastin is the building block of elastin, a key component of the skin, arteries and lungs that gives tissue its elasticity. Institute of Polymers, Composites and Biomaterials, National Research Council (IPCB-CNR), Italy, Washington University in St. Louis, United States. Thus, elastin is responsible, in great part, for the properties of elastic fibers. With this approach, Allergan has built one of the broadest development pipelines in the pharmaceutical industry. doi: 10.1021/bi0610092, Cordier, P., Tournilhac, F., Souli-Ziakovic, C., and Leibler, L. (2008). 67-kD elastin-binding protein is a protective companion of extracellular insoluble elastin and intracellular tropoelastin. 289, 14671477. doi: 10.1007/s10973-014-4254-9, Debelle, L., and Tamburro, A. M. (1999). doi: 10.1267/ahc.10026, Yang, A. S., and Honig, B. (2020). 282, 1248412491. doi: 10.1007/s004030050227, Tamburro, A. M., Bochicchio, B., and Pepe, A. Nat. Allergan is an industry leader in Open Science,a model of research and development, which defines our approach to identifying and developing game-changing ideas and innovation for better patient care. Further to this, the flexibility of the hydrophobic domains may also play a key role in self-assembly. *Correspondence: Anthony S. Weiss, tony.weiss@sydney.edu.au, These authors have contributed equally to this work, Fibrous Assemblies: From Synthesis and Nanostructure Characterization to Materials Development and Application, Front. For example, the highly flexible domains 25 that were noted to generate a twisting motion in N-terminus, were positioned beside domain 6, a relatively immobile region that may assist in stabilizing the subsequent regions. J. Therm. The isoform-function theory is further reinforced by the presence of two different ELN genes within teleosts that are differentially expressed both spatially and temporally during development (Miao et al., 2007). Targeted modulation of tropoelastin structure and assembly. Additionally, coarse-graining the full-atomistic model has allowed for the examination of mesoscale tropoelastin assembly and, in particular, deciphered the orientation of tropoelastin molecules that occurs during early stage assembly (inset image) (Tarakanova et al., 2019a). Total synthesis and expression in Escherichia coli of a gene encoding human tropoelastin. The hydrophobic domains are involved in coacervation and the hydrophilic domains are used for cross-linking. Molecular model for elastin structure and function. doi: 10.1016/j.matbio.2009.10.003, Tu, Y., Wise, S. G., and Weiss, A. S. (2010). Natl. A. 264, 88878891. (2019). (2005). (2013). The hydrophobic domains vary in length, with the majority of the shorter (95 residues) domains occurring near the N-terminus, while the longer (up to 55 residues) domains are found within tropoelastins central and C-terminal regions (Indik et al., 1989). Structure 14, 16671676. Chemistry 10, 31663176. Structure of the elastin gene and alternative splicing of elastin mRNA: implications for human disease. Microfibrils comprise multiple proteins, of which fibrillin-1 is the most common. Int. Integrins are a major class of cell surface receptor family, of which tropoelastin has been found to interact with two types: v3 (Rodgers and Weiss, 2004) and v5. Pathol. Fibrillin-rich microfibrils of the extracellular matrix: ultrastructure and assembly. 126, 563574. (2015). Indeed, cryo-EM was recently reported to have a lower molecular size limit of approximately 50 kDa, however, it has not yet been successfully applied to characterize tropoelastin (Murata and Wolf, 2018). Increased cyclic GMP levels lead to a stimulation of elastin production in ligament fibroblasts that is reversed by cyclic AMP. The bifunctional cross-links can undergo further condensation to form tetrafunctional desmosine or isodesmosine (Partridge, 1966). Coacervation optimally occurs at physiological temperature, however, in vitro coacervation can also occur at lower temperatures depending on experimental conditions and the choice of tropoelastin isoform or derivative (Yeo et al., 2011). Exp. 43, 131138. Together, we build bridges, power ideas, act fast and drive results for our customers and patients around the world by always doing what is right.

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