Acad. Human tropoelastin improves rat heart function postmyocardial infarction and could potentially be used to treat heart failure. Tropoelastins flexibility does not allow it to pack into a crystal lattice and its size renders it too complex to assign atomic interactions using nuclear magnetic resonance (NMR) on a global level (Tamburro et al., 2003, 2006; Bochicchio et al., 2004; Pepe et al., 2008). Exp. Furthermore, as integrins are involved in the remodeling of the ECM (Bonnans et al., 2014), this is consistent with a model where the tropoelastin-integrin interaction forms part of the wound repair process. Solving tropoelastins global structure (Baldock et al., 2011) allowed for 3D mapping on tropoelastin of the approximate locations of domains 10, 19, and 25, which were the first unequivocally cross-linked domains to be discovered (Brown-Augsburger et al., 1995). Chem. Tropoelastin is a unique protein with biochemical and physical properties that allow it to rapidly self-assemble into fibrous structures. Collapse Section. Cross-linking domains are capable of modulating self-assembly when incorporated into peptides and biomaterials derived from tropoelastins hydrophobic domains. The alignment of these three domains indicates that at least two tropoelastin molecules are required to form this tetrafunctional cross-link, thus, giving rise to the head-to-tail model of assembly involving the growth of a linear chain that can assemble laterally to form sheets and eventually form spherules (Baldock et al., 2011). (2017). Chem. Domains 12 to 16 of tropoelastin promote cell attachment and spreading through interactions with glycosaminoglycan and integrins alphaV and alpha5beta1. Molecular docking studies utilizing tropoelastin and the 3D structure of LOX1 (Vallet et al., 2018) may assist in our understanding as to whether the enzyme has a preference for modifying particular tropoelastin residues. doi: 10.1021/bi981641y, Kozel, B. A Study to Evaluate the Efficacy of ELAPR002f in Females and Males With Positively charged lysine residues in domains 17 were identified to interact with negatively charged HS, most likely via ionic interactions (Lee et al., 2017). Sequences and domain structures of mammalian, avian, amphibian and teleost tropoelastins: clues to the evolutionary history of elastins. On a per-share basis, the Irving, Texas-based company said it had profit of 1 cent. Pharm. Even after being able to produce recombinant tropoelastin at scales suited to characterization studies, traditional techniques have not yet produced an experimentally verified atomistic structure (Martin et al., 1995; Tarakanova and Buehler, 2013). Fell muir lecture: collagen fibril formation in vitro and in vivo. Matrix Biol. All rights reserved. The human ELN gene is located on the long arm of chromosome 7q11.2 and comprises of 34 exons nestled between lengthy introns (Indik et al., 1987, 1989; Bashir et al., 1989). III. For example, models involving single point mutations at negatively charged residues demonstrated both regional and global destabilization of tropoelastins structure, which were validated by SAXS structures (Yeo et al., 2012; Tarakanova et al., 2018). Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon. Transient tropoelastin nanoparticles are early-stage intermediates in the coacervation of human tropoelastin whose aggregation is facilitated by heparan sulfate and heparin decasaccharides. Completion of the transition is subject to customary closing conditions, including review by Australias Foreign Investment Review Board. doi: 10.1038/nrm3904, Bressan, G. M., Castellani, I., Giro, M. G., Volpin, D., Fornieri, C., and Pasquali Ronchetti, I. Allergan plc (NYSE: AGN), headquartered in Dublin, Ireland, is a bold, global biopharmaceutical company. It's a major component of tissues in your body that require stretchiness, like your lungs, bladder, large blood vessels and some ligaments. Unlike other companies that use paid endorsements and questionable data, NULASTIN science is proven by 3rd party clinical evaluation. Chem. Biopolymers 103, 563573. PLoS One 7:e46130. Tropoelastin was revealed to be an asymmetric molecule with distinct N- and C-terminal regions that are respectively referred to as the head and foot of the molecule. Allergan acquired Elastagen primarily for the injectable product portfolio (acne scars/stretch marks aesthetics). Lysinonorleucine. 28, 432441. Together, these two properties can be tuned and exploited to give rise to an increasing number of novel biomaterials for tissue engineering and regenerative medicine, which have been recently reviewed elsewhere (Wang et al., 2020; Wen et al., 2020). These ordered structures can include -helices and -structures (Vrhovski et al., 1997), which depend on the amino acid content and arrangement of domains (He et al., 2012; Reichheld et al., 2014, 2017; Muiznieks et al., 2015) and the choice of solvent (Reiersen and Rees, 2000; Muiznieks et al., 2015). doi: 10.1074/jbc.M212715200, Kumashiro, K. K., Ho, J. P., Niemczura, W. P., and Keeley, F. W. (2006). Total synthesis and expression in Escherichia coli of a gene encoding human tropoelastin. Approximately 90% of tropoelastins lysines undergo modification and/or participate in cross-links, indicating that mature elastin is extensively cross-linked (Kozel et al., 2003; Schmelzer et al., 2019). Elastin is one of the most abundant proteins in your body. Tropoelastin promotes cell attachment and migration of several cell types including fibroblasts, endothelial cells and mesenchymal stem cells. Interactions of fibrillin-1 with heparin/heparan sulfate, implications for microfibrillar assembly. Genet. Pharmacol. Elastic fibers are present in the extracellular matrix (ECM) of vertebrate tissues, such as the skin, lungs, cardiovascular system, cartilage, and tendons. J. CICADA TURNS 20: How synthetic skin biotech Elastagen changed lives Allergans success is powered by our global colleagues commitment to being Bold for Life. Fabricating organized elastin in vascular grafts. Coacervation characteristics of recombinant human tropoelastin Biochim. doi: 10.1073/pnas.1812951116, Yue, K., Li, X., Schrobback, K., Sheikhi, A., Annabi, N., Leijten, J., et al. FEBS J. Weiss Lab Home IRVING, Texas (AP) IRVING, Texas (AP) Fluor Corp. (FLR) on Tuesday reported fourth-quarter net income of $9 million, after reporting a loss in the same period a year earlier. J. Biol. (1988). Elastic fiber formation: a dynamic view of extracellular matrix assembly using timer reporters. However, higher resolution data were required to map out its elusive properties and performance within a hierarchical assembly (Tarakanova et al., 2018; Ozsvar et al., 2019). Furthermore, tropoelastins hydrophobic and cross-linking domains are arranged in alternating patterns throughout the majority of the molecule, giving rise to both inter- and intra-domain level repetition. Cross-linking domains can be subdivided into KP or KA domains, which denote the amino acids (proline or alanine, respectively) that are adjacent to the lysines (Figure 1). (2013). 19:e1800250. Caterpillar | Caterpillar to Relocate Global Headquarters to Dallas doi: 10.1046/j.1432-1327.1999.00891.x, Yamauchi, Y., Tsuruga, E., Nakashima, K., Sawa, Y., and Ishikawa, H. (2010). Domain 36 of tropoelastin in elastic fiber formation. 10 Endothelial cells, vascular smooth muscle cells, and adventitial fibroblasts produce tropoelastin during the late Proline-poor hydrophobic domains modulate the assembly and material properties of polymeric elastin. Mechanism of helix induction by trifluoroethanol: a framework for extrapolating the helix-forming properties of peptides from trifluoroethanol/water mixtures back to water. (1981). J. Mol. Albert, E. N. (1972). Bull. Fluor: Q4 Earnings Snapshot. 9:643110. doi: 10.3389/fbioe.2021.643110. (2014). Domains 2736 make up tropoelastins foot, which are labeled as such due to their spatial arrangement, forming an almost claw-like component of the molecule. 31, 261272. Foster, J. 9:eaai7466. 11 Articles, This article is part of the Research Topic, Tropoelastin-Cell Receptor Interactions and Implications for Assembly, https://doi.org/10.3389/fbioe.2021.643110, Creative Commons Attribution License (CC BY). doi: 10.1016/0378-1119(94)00848-m, McLaughlin, P. J., Chen, Q., Horiguchi, M., Starcher, B. C., Stanton, J. doi: 10.1074/jbc.M104985200, Toonkool, P., Jensen, S. A., Maxwell, A. L., and Weiss, A. S. (2001). Ann. doi: 10.1083/jcb.68.3.411, Noda, K., Dabovic, B., Takagi, K., Inoue, T., Horiguchi, M., Hirai, M., et al. The conversion of a single lysine to an allysine results in structural stabilization, which may serve as a checkpoint during self-assembly to ensure that molecules incapable of forming multiple cross-links are not incorporated into the growing chain. Modeling has been verified using wet-bench methodologies, forming a robust suite of complementary methodologies that will undoubtedly become more prevalent for exploring the assembly of biological fibers over time. doi: 10.1096/fj.201801860RR, Schrader, C. U., Heinz, A., Majovsky, P., Karaman Mayack, B., Brinckmann, J., Sippl, W., et al. Biol. This suggests a high level of conformational sampling during this phase of coacervation, indicating that the flexibility of tropoelastin plays a key role in assembly that may persist, to some extent, into later stages of assembly (Reichheld et al., 2020). Molecular model of human tropoelastin and implications of associated mutations. Elastagen has received investment from an international syndicate of venture groups including AmorePacific Ventures, Brandon Capital, Cell Innovation Partners, Cicada Innovations, GBS Ventures, Korea Investment Partners and the Wellcome Trust. Shape of tropoelastin, the highly extensible protein that - PNAS It has been postulated that the interaction between tropoelastin and cell surface proteoglycans is part of the assembly process of elastin before it is deposited on microfibrils. 252, 351365. Elastin-like polypeptides as models of intrinsically disordered proteins. The cross-linking domains are defined by lysines, which are responsible for the formation of durable bi-, tri-, and tetrafunctional cross-links within mature elastin. Micron 32, 185200. They can be categorized as either hydrophobic or cross-linking based on their functionality and amino acid content (Figure 1). DEERFIELD, IL - Caterpillar Inc. (NYSE: CAT) today announced it will move its global headquarters to the company's existing office in Irving, Texas, from its current location in Deerfield, Illinois. 87, 18281834. Bashir, M. M., Indik, Z., Yeh, H., Ornstein-Goldstein, N., Rosenbloom, J. C., Abrams, W., et al. doi: 10.1002/mabi.201800250, Tiedemann, K., Batge, B., Muller, P. K., and Reinhardt, D. P. (2001). 289, 489492. A., and Rucker, R. B. Interactions with these integrins on the surface of mesenchymal stem cells, either through surface bound or as soluble tropoelastin, promote MSC proliferation and phenotypic maintenance via FAK and PKB/AKT (Yeo and Weiss, 2019). Sequence and structure determinants for the self-aggregation of recombinant polypeptides modeled after human elastin. 289, 14671477. "We believe it's in the best strategic interest of the company to make this move, which supports Caterpillar's strategy for profitable . U.S.A. 108, 43224327. Simul. Allergan Plc, a $15.9b provider of medical aesthetics, biosimilars, and over-the-counter pharmaceutical products will acquire Elastagen Pty Ltd., a provider of advanced tissue repair platform based on tropoelastin (gives tissue its elasticity) for $95m.The acquisition adds proprietary injectable products to Allergan's existing portfolio. A., Torres, A. R., Alvarez, V. L., and Janata, J. Figure 3. 258, 118. J. Biol. Insights into the structure and dynamics of lysyl oxidase propeptide, a flexible protein with numerous partners. 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). (2015). (2019a). All authors contributed to writing and editing the review. 37, 698702. The process of tropoelastin aggregation is initially reversible, as spherules dissipate if the temperature is lowered (Clarke et al., 2006), however, maintenance of a physiological temperature results in maturation, which is indicated by spherule coalescence and the irreversible formation of fibrillar structures (Cox et al., 1974; Bressan et al., 1983; Mithieux et al., 2005). 2:e1501145. Future investigations will allow the bridging of the gap between mesoscale simulations and microscopically observed coacervation (Clarke et al., 2006). Developmental changes of tropoelastin synthesis by rat pulmonary fibroblasts and effects of dexamethasone. Biochemistry 42, 1334713362. The hydrophobic domains contain repetitions and variations of Val-Pro-Gly-Val-Gly motifs (Figure 1), resulting in the aforementioned low complexity of sequence (Foster et al., 1973; Gray et al., 1973). Parameter, Testing, and Method. Biochim. Proc. This model revealed that tropoelastin maintains a canonical or average structure based on the distribution of its possible conformations in spite of its flexible nature (Figure 2), as well as the possible roles that local structures play in biological processes, specifically, elastogenesis (Tarakanova et al., 2019b). Attempts to characterize tropoelastins structure have seen a gradual shift from the belief that tropoelastins domains have fixed structures, to understanding that the majority of its domains are capable of transitioning between random coils and transient ordered structures. Proc. *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. Fluor: Q4 Earnings Snapshot | AP News Single nucleotide polymorphisms and domain/splice variants modulate assembly and elastomeric properties of human elastin. 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. Tropoelastin, the soluble precursor to elastin, and the degradation products of fragmented elastic fibers also have important chemical signaling properties. Founder, Elastagen Pty Ltd (sold to Allergan/AbbVie . Elastic fibers are an important component of the extracellular matrix, providing stretch, resilience, and cell interactivity to a broad range of elastic tissues. U.S.A. 84, 56805684. Coacervation of tropoelastin. Structural changes and facilitated association of tropoelastin. doi: 10.1016/j.bbagen.2017.07.020, Myers, B., Dubick, M., Last, J. 10, 441454. The study is designed to evaluate the efficacy of two formulations of a cross-linked tropoelastin matrix given the product codes ELAPR002f (collectively referred to as ELAPR or ELAPR002) for the treatment of rolling atrophic acne scars when administered as intradermal implants. 79, 277284. doi: 10.1016/j.biomaterials.2017.04.050, Keywords: elastin, elastic fibers, tropoelastin, computational modeling, assembly, Citation: Ozsvar J, Yang C, Cain SA, Baldock C, Tarakanova A and Weiss AS (2021) Tropoelastin and Elastin Assembly. doi: 10.1021/acs.biomac.0c00546, Bochicchio, B., Floquet, N., Pepe, A., Alix, A. J., and Tamburro, A. M. (2004). The ELN gene provides instructions for making a protein called tropoelastin. Allergen Acquires Elastagen - pharmasalmanac.com Tropoelastin massively associates during coacervation to form quantized protein spheres. Tropoelastin Improves Post-Infarct Cardiac Function 58, 270277. Our Juvederm collection of fillers has sales of over $1 billion globally and is one of the fastest growing parts of our Aesthetics business, said Bill Meury, Chief Commercial Officer at Allergan. Tropoelastin #5052. Res. Mater. doi: 10.1111/iep.12224, Kentsis, A., and Sosnick, T. R. (1998). Tropoelastin is characterised by alternating hydrophobic and hydrophilic domains and is highly flexible. doi: 10.1021/bi9707133, MacEwan, S. R., Weitzhandler, I., Hoffmann, I., Genzer, J., Gradzielski, M., and Chilkoti, A. Synthesis and properties of crosslinked recombinant pro-resilin. Elastin synthesis during perinatal lung development in the rat. Natl. Human ELN gives rise to a broad variety of splice isoforms, with alternative splicing being observed with exons 22, 23, 24, 26A, 32, and 33 (Fazio et al., 1988; Parks et al., 1992) that result in 13 known human isoforms of the mature tropoelastin protein (Reichheld et al., 2019). This temperature is also known as the transition temperature. To get started with texting, you will need: Your phone number Tropoelastin - an overview | ScienceDirect Topics 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). The presence of tropoelastin spherules fusing to fibrils has been noted in native tissue, demonstrating marked similarities between in vitro and in vivo coacervation (Haust et al., 1965; Albert, 1972; Kozel et al., 2006). doi: 10.1016/0304-4165(83)90357-4, Narayanan, A. S., Sandberg, L. B., Ross, R., and Layman, D. L. (1976). EBP plays two roles in the assembly of elastin. The elasticity of organs and tissues in vertebrates is due to the presence of elastin, and an insoluble protein whose soluble monomer, tropoelastin, is enzymatically cross-linked through -amino groups of lysine residues. Remodelling the extracellular matrix in development and disease. Additionally, elastin is remarkably durable as it is primarily deposited during prenatal development and childhood, and is rarely synthesized during adulthood. Natl. Tropoelastin - PubMed Self-healing and thermoreversible rubber from supramolecular assembly. J. Biol. (2005). Dermatol. Am. Biochemistry 8, 28332837. 15, 786801. 3, 4 Elastin has a very low rate of turnover, so it . doi: 10.1002/bip.1981.360200611. 281, 2375723765. Elastagen Pty Ltd, a clinical stage company developing medical device products based on recombinant tropoelastin, today announced that it has entered into a definitive agreement under which Allergan plc, a leading global biopharmaceutical company, has agreed to acquire Elastagen. Soluble matrix protein is a potent modulator of mesenchymal stem cell performance. Modulative effects are also observed within full length tropoelastin, where disruptions to domain 26 diminish self-assembly (Jensen et al., 2000), highlighting the context of primary sequence on higher order structures. Elastin is heterogeneously cross-linked. Meanwhile, modifications to the full-atomistic model have revealed the mechanisms that contribute to aberrant fiber structure (Tarakanova et al., 2018) that have been hypothesized to predispose patients to diseases such as acquired cutis laxa (Hu et al., 2006). It is likely that, as a general rule, integrin binding to tropoelastin is mediated via GAGs, which is facilitated by the repetition of tropoelastins primary sequence and the surface exposure of positively charged similar domains (Lee et al., 2017; Bochicchio et al., 2021). Forty tropoelastin molecules were subjected to simulations using a MARTINI-based coarse-grained model, integrated with an elastic network model (Tarakanova et al., 2019a). Homology models for domains 21-23 of human tropoelastin shed light on lysine crosslinking. J. Struct. Today Biol. Injectable biomaterial compositions formed from tropoelastin for tissue repair and restoration. Cell Physiol. 7:32. doi: 10.3389/fphar.2016.00032, Schmelzer, C. E. H., Heinz, A., Troilo, H., Lockhart-Cairns, M. P., Jowitt, T. A., Marchand, M. F., et al. (2012). The amino acid sequence of domain 36 is unique; furthermore, its sequence confers a positively charged C-terminus comprising lysines between positively charged arginines, forming a RKRK sequence (Vrhovski et al., 1997). doi: 10.1016/0005-2795(73)90368-1, Franzblau, C., Faris, B., and Papaioannou, R. (1969). Amino acid conformational preferences and solvation of polar backbone atoms in peptides and proteins. Tropoelastin: a novel marker for plaque progression and instability. 280, 4093940947. Modulation by elastin peptide VGVAPG of cell proliferation and elastin expression in human skin fibroblasts. Int. 28, 379382. FEBS J. Direct observation of structure and dynamics during phase separation of an elastomeric protein. In addition to its involvement in molecular elasticity, the flexibility of tropoelastin also a key requirement for self-assembly into elastin, with mutations that perturb this having detrimental effects on tissue (Yeo et al., 2016, 2017). Circ. 207, 8796. Another region of note is domain 36, which contains lysines but does not participate in cross-linking (Hedtke et al., 2019). U.S.A. 116, 20422051. J. Biomol. This product is generally used in vitro as a substrate scaffold to enhance cell attachment, adherence and proliferation. 84, 6880. Proc. Tropoelastin has 2 alternating domains: (1) hydrophilic, cross-linked, domains rich in Lys and Ala; and (2) hydrophobic domains (responsible for elasticity) rich in Val, Pro, and Gly, which often occur in repeats of VPGVG or VGGVG. Elastic fibers are eventually formed after extensive cross-linking through a process termed maturation (Yeo et al., 2016). 25, 10231029. Lyophilized Powder. (1983). Visconti, R. P., Barth, J. L., Keeley, F. W., and Little, C. D. (2003). Biophys. Trifluoroethanol may form a solvent matrix for assisted hydrophobic interactions between peptide side chains. Elastin - Wikipedia Biomaterials 127, 4960. Annabi, N., Zhang, Y. N., Assmann, A., Sani, E. S., Cheng, G., Lassaletta, A. D., et al. 26, 17001709. Powered by Madgex Job Board Software. doi: 10.1016/j.matbio.2006.10.002, Dyksterhuis, L. B., and Weiss, A. S. (2010). doi: 10.1016/s1357-2725(98)00098-3, Duca, L., Blanchevoye, C., Cantarelli, B., Ghoneim, C., Dedieu, S., Delacoux, F., et al. Tropoelastins primary sequence is low in complexity and contains repetitive motifs. Reichheld, S. E., Muiznieks, L. D., Huynh, Q., Wang, N., Ing, C., Miao, M., et al. (2019). Production of recombinant human tropoelastin: Characterization and Computational smart polymer design based on elastin protein mutability. doi: 10.1016/j.matbio.2006.08.258, Clarke, A. W., Arnspang, E. C., Mithieux, S. M., Korkmaz, E., Braet, F., and Weiss, A. S. (2006). Natl. Molecular model for elastin structure and function. doi: 10.1074/jbc.RA118.004322, Shapiro, S., Endicott, S., Province, M., Pierce, J., and Campbell, E. (1991). Med. doi: 10.1016/j.cis.2010.10.003, Yeo, G. C., Tarakanova, A., Baldock, C., Wise, S. G., Buehler, M. J., and Weiss, A. S. (2016). Biophys. Allergan is focused on developing, manufacturing and commercializing branded pharmaceutical, device, biologic, surgical and regenerative medicine products for patients around the world. Biopolymers 107:e23007. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). doi: 10.1016/j.str.2006.09.008, Rauscher, S., and Pomes, R. (2017). Bochicchio, B., Yeo, G. C., Lee, P., Emul, D., Pepe, A., Laezza, A., et al. Elastagen's technology is based on human tropoelastin . Trends towards maximal association are apparent when each of these parameters is varied. Targeted modulation of tropoelastin structure and assembly. The prevention of early self-aggregation in vitro is thought to be mediated by chaperone proteins (Hinek and Rabinovitch, 1994; Miao et al., 2013). Chem. 396, 870873. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. J. Biol. doi: 10.1016/j.febslet.2015.08.029, Rodgers, U. R., and Weiss, A. S. (2004). Tropoelastin aggregates at physiological temperature due to interactions between hydrophobic domains in a process called coacervation. J. Biochem. The hydrophobic domain 26 of human tropoelastin is unstructured in solution. (1989). (1965). Mol. A novel cell adhesion region in tropoelastin mediates attachment to integrin alphaVbeta5. doi: 10.1016/s0022-5320(83)80021-5, Broekelmann, T. J., Kozel, B. Matrix Biol. The stiffness that arose due to amino acid substitutions partially determined resultant secondary structure which, in turn, impacted assembly (Prhashanna et al., 2019). Res. doi: 10.1016/j.biomaterials.2017.01.041, Tarakanova, A., Ozsvar, J., Weiss, A. S., and Buehler, M. J. J. Biol. Overview of the computational and experimental methodologies that have recently contributed to our understanding of elastic fiber assembly. Cooperativity between the hydrophobic and cross-linking domains of elastin. doi: 10.1016/j.matbio.2009.07.003, Mithieux, S. M., Wise, S. G., Raftery, M. J., Starcher, B., and Weiss, A. S. (2005). 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. With leaps in the improvement of cryogenic electron microscopy to characterize flexible molecules, we predict that this approach will contribute to a deeper understanding of tropoelastin structure and self-assembly in the context of endogenous fiber formation and biomaterials fabrication. 22, 109121. These remarkable properties arise from its sequence and structure, which render tropoelastin structurally highly flexible but not disordered (Tarakanova et al., 2018). Structural analysis of photocrosslinkable methacryloyl-modified protein derivatives. (2018). Plus 2:100002. doi: 10.1016/j.mbplus.2019.03.001, Parks, W. C., Roby, J. D., Wu, L. C., and Grosso, L. E. (1992). Cell Biol. (2015). 300, 13351359. Such models could be used in conjunction with the full molecular model of tropoelastin to examine the self-assembly of discrete regions to understand the impacts of amino acid substitutions in disease. Matrix Biol. 150, 154162. Tropoelastin (TE) is the main (>90%) component of elastin, wherein crosslinked assembled coacervates of TE are exposed to lysyl oxidases and interact with microfibrils to expand elastin fibers. Sci. Matrix 12, 156162. Elastagens tropoelastin is identical to that present in human tissue, and has many potential clinical applications, including treatment for acne scars, stretch marks, aesthetic skin repair and surgical wound repair. Polymorphisms in the human tropoelastin gene modify in vitro self-assembly and mechanical properties of elastin-like polypeptides.
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