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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). doi: 10.1021/bi00835a022, Lockhart-Cairns, M. P., Newandee, H., Thomson, J., Weiss, A. S., Baldock, C., and Tarakanova, A. Fed. On a per-share basis, the Irving, Texas-based company said it had profit of 1 cent. Elastagen Pty Ltd, a clinical stage company developing medical device products based on recombinant tropoelastin, today announced. J. Biol. Combinations of these two amino acids result in domains that undergo rapid conformational sampling (Rauscher and Pomes, 2017), which, if perturbed toward a conformation that gravitate toward stability, will assemble into highly ordered amyloid-like fibrils that are not elastomeric (Rauscher et al., 2006; Roberts et al., 2015). doi: 10.1016/j.jsb.2004.11.005, Muiznieks, L. D., Jensen, S. A., and Weiss, A. S. (2003). Adv. 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. US8974803B2 - Injectable biomaterials - Google Patents Domain 26 of tropoelastin plays a dominant role in association by coacervation. Tropoelastins hydrophobic domains are predominantly responsible for the random coil content of the monomer, and are the result of the unique pairing of proline and glycine pairs that are interspersed throughout the majority of hydrophobic domains (Rauscher and Pomes, 2017). Cross-linking domains are capable of modulating self-assembly when incorporated into peptides and biomaterials derived from tropoelastins hydrophobic domains. Elastin is heterogeneously cross-linked. Biochem. doi: 10.1203/00006450-199010000-00015, Nonaka, R., Sato, F., and Wachi, H. (2014). AW is the Scientific Founder of Elastagen Pty. 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. doi: 10.1021/bi9707133, MacEwan, S. R., Weitzhandler, I., Hoffmann, I., Genzer, J., Gradzielski, M., and Chilkoti, A. Today Biol. doi: 10.1111/j.1749-6632.1991.tb17013.x, Mecham, R. P., Levy, B. D., Morris, S. L., Madaras, J. G., and Wrenn, D. S. (1985). Acta 303, 363369. 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. (2006). It was first hypothesized that tropoelastin assembles in a head-to-tail manner similar to that of other ECM proteins such as collagen, which assembles into fibrils that subsequently associate laterally to form sheets and thicker fibers (Kadler, 2017). Elastin is a critical skin protein consisting of crosslinked tropoelastin. Multiple copies of the tropoelastin protein attach to one another and are processed to form a mature protein called elastin. Tropoelastins amino acid sequence predominantly consists of non-polar residues including glycine, valine, alanine, and proline (Debelle and Tamburro, 1999). For example, their inclusion in peptides derived from hydrophobic domains confers decreased times taken for self-assembly, most likely due to their favorable interaction with aqueous solvent (Miao et al., 2003). (2005). Elastin: molecular description and function. J. Biol. Its hydrophobic (pink) and cross-linking (blue) domains consist of repetitive motifs that contribute uniquely to elastin assembly. Elastic fibers provide tissues with mechanical resilience, durability, and cell interactivity, which support a diverse range of specialized functionality. Allergan is focused on developing, manufacturing and commercializing branded pharmaceutical, device, biologic, surgical and regenerative medicine products for patients around the world. A., Ishibashi, H., Werneck, C. C., Keeley, F. W., Zhang, L., et al. Fibulin-4 and -5, but not fibulin-2, are associated with tropoelastin deposition in elastin-producing cell culture. Communication: coacervation of tropoelastin results in fiber formation. Tropoelastin, the soluble precursor to elastin, and the degradation products of fragmented elastic fibers also have important chemical signaling properties. Elastic fiber formation: a dynamic view of extracellular matrix assembly using timer reporters. Upon secretion tropoelastin has the propensity to self-aggregate through a process known as coacervation. doi: 10.1096/fj.201801860RR, Schrader, C. U., Heinz, A., Majovsky, P., Karaman Mayack, B., Brinckmann, J., Sippl, W., et al. doi: 10.1016/j.jsb.2005.02.005, Martin, S. L., Vrhovski, B., and Weiss, A. S. (1995). Biotechnol., 25 February 2021, View all However, there are aspects of this model that warrant further investigation. 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. (2016). Matrix Biol. With the acquisition, Allergan will begin developing a new line that incorporates tropoelastin in the injectable's formula. 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. 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. 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. Biotechnol. 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). Moreover, fibulins are essential for elastic fiber directionality, as fibroblasts with fibulin-4 and -5 knockdowns generate poorly formed elastic fibers (Yamauchi et al., 2010), and fibulin-4 / mice display aberrant, poorly cross-linked, and non-fibrous elastin (McLaughlin et al., 2006). 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. doi: 10.1038/sj.jid.5700047, Indik, Z., Yeh, H., Ornstein-Goldstein, N., Kucich, U., Abrams, W., Rosenbloom, J. C., et al. Rep. 8, 116. doi: 10.1016/j.ajhg.2009.09.013. Natl. Tropoelastin. Aaron, B., and Gosline, J. It's a major component of tissues in your body that require stretchiness, like your lungs, bladder, large blood vessels and some ligaments. Elastin as a random-network elastomer: a mechanical and optical analysis of single elastin fibers. doi: 10.1038/nature04085. doi: 10.1016/j.matbio.2006.09.011, Miao, M., Reichheld, S. E., Muiznieks, L. D., Huang, Y., and Keeley, F. W. (2013). Specific instructions are found in the Directions for Use. Trifluoroethanol promotes helix formation by destabilizing backbone exposure: desolvation rather than native hydrogen bonding defines the kinetic pathway of dimeric coiled coil folding. doi: 10.1016/s1357-2725(98)00098-3, Duca, L., Blanchevoye, C., Cantarelli, B., Ghoneim, C., Dedieu, S., Delacoux, F., et al. Protein Eng. Fibrillin-rich microfibrils of the extracellular matrix: ultrastructure and assembly. 41, 494497. Biol. 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. doi: 10.1126/scitranslmed.aai7466, PubMed Abstract | CrossRef Full Text | Google Scholar, Avbelj, F. (2000). HS, which is present on cell surface proteoglycans (syndecans and glypicans), interacts strongly with tropoelastin (Cain et al., 2005). 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. Cryo-electron microscopy for structural analysis of dynamic biological macromolecules. EDPs can modulate an array of signal pathways (Scandolera et al., 2016), but full-length tropoelastin does not trigger pathways through the ERC. Sci. 27, 441450. The elastin receptor complex: a unique matricellular receptor with high anti-tumoral potential. (2012). "We believe it's in the best strategic interest of the company to make this move, which supports Caterpillar's strategy for profitable . Transl. Biol. The SAXS/SANS global shape of tropoelastin (Baldock et al., 2011) has been used to validate the full-atomistic computational model of tropoelastin through a geometric and topological comparison (Tarakanova et al., 2018). doi: 10.1038/nature06669, Cox, B. Transient tropoelastin nanoparticles are early-stage intermediates in the coacervation of human tropoelastin whose aggregation is facilitated by heparan sulfate and heparin decasaccharides. Sci. Exp. 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). Matrix Biol. They can be categorized as either hydrophobic or cross-linking based on their functionality and amino acid content (Figure 1). Tropoelastin monomers undergo self-assembly upon reaching the transition temperature through the aggregation of their hydrophobic domains (Wise et al., 2014). doi: 10.1016/0014-4800(65)90015-8, He, D., Chung, M., Chan, E., Alleyne, T., Ha, K. C. H., Miao, M., et al. 10, 441454. Copyright 2021 Ozsvar, Yang, Cain, Baldock, Tarakanova and Weiss. Further to this, the flexibility of the hydrophobic domains may also play a key role in self-assembly. J. Biol. Stem cell growth accelerated by tropoelastin protein The N-terminal head caps an extended coil region that consists of domains 218. Figure 2. doi: 10.1111/febs.14929, Hinderer, S., Shena, N., Ringuette, L. J., Hansmann, J., Reinhardt, D. P., Brucker, S. Y., et al. 13, 739743. The first is an intracellular role as a tropoelastin chaperone and the second is as part of the elastin receptor complex (ERC). Insights into the structure and behavior of tropoelastin have translated into increasingly sophisticated . Tropoelastin | Circulation: Cardiovascular Imaging The coacervate is made insoluble by irreversible crosslinking. Bioeng. Chemistry 10, 31663176. Reichheld, S. E., Muiznieks, L. D., Huynh, Q., Wang, N., Ing, C., Miao, M., et al. doi: 10.1016/j.actbio.2013.08.003, Wu, W. J., and Weiss, A. S. (1999). doi: 10.1016/s0021-9258(19)83613-x, Miao, M., Bellingham, C. M., Stahl, R. J., Sitarz, E. E., Lane, C. J., and Keeley, F. W. (2003). The advantage of coarse-grained methodologies is that they allow for the simulation of timescales of large molecular systems on the order of microseconds, which are otherwise computationally infeasible with classical full-atomistic molecular dynamics. For this injection, the researchers used a new . doi: 10.1016/j.matbio.2009.07.003, Mithieux, S. M., Wise, S. G., Raftery, M. J., Starcher, B., and Weiss, A. S. (2005). Genet. 2:e1501145. 276, 4457544580. Although alanine tracts within other proteins are predisposed to -helix formation (Yang and Honig, 1995; Avbelj, 2000), high helical content within tropoelastins KA domains was primarily demonstrated to persist in solvents that stabilize secondary structure, such as trifluoroethanol, rather than aqueous solution (Luo and Baldwin, 1997; Tamburro et al., 2006). Pediatr. Tropoelastin is characterised by alternating hydrophobic and hydrophilic domains and is highly flexible. Tropoelastin Improves Post-Infarct Cardiac Function (2013). Sci. Tropoelastin is typically used as a thin coating on tissue culture surfaces. Polymorphisms in the human tropoelastin gene modify in vitro self-assembly and mechanical properties of elastin-like polypeptides. Elastin binding protein (EBP) is a splice variant of -galactosidase, that recognizes the repetitive hydrophobic sequences (VGVAPG) of tropoelastin (Tajima et al., 1997). Acad. 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. 264, 88878891. J. Mol. doi: 10.1074/jbc.M510833200, Lee, P., Bax, D. V., Bilek, M. M., and Weiss, A. S. (2014). Acad. The smallest amino acid, glycine is known to promote flexibility within local structures due to lack of steric hindrance, whereas prolines restrictive sidechain inhibits conformational sampling and disrupts the formation of prolonged secondary structures (Roberts et al., 2015). A., Starcher, B. C., and Urry, D. W. (1974). The stiffness that arose due to amino acid substitutions partially determined resultant secondary structure which, in turn, impacted assembly (Prhashanna et al., 2019). Weiss Lab Home Biochim. 282, 1248412491. J. Biol. 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). Targeted modulation of tropoelastin structure and assembly. Chem. Macromol. 120, 419426. Gene 154, 159166. Sci. 68, 411419. 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. Codistribution analysis of elastin and related fibrillar proteins in early vertebrate development. Elastagen was one of the inaugural recipients of MDF funding in 2013 and will be the first to successfully repay the funding amount. In addition to interacting with tropoelastin, fibulin-4 and -5 are capable of also binding LOX and fibrillin-1 and, thus, have key roles in facilitating elastogenesis (Hinderer et al., 2015). Frontiers | Tropoelastin and Elastin Assembly Mater. doi: 10.1007/s10973-014-4254-9, Debelle, L., and Tamburro, A. M. (1999). Micron 32, 185200. doi: 10.1074/jbc.M113.533893, Reiersen, H., and Rees, A. R. (2000). A Study to Evaluate the Efficacy of ELAPR002f in Females and Males With Unsubstituted models are also critical to understanding self-assembly. Further down the molecule, the cell-interactive C-terminus was noted to be highly flexible, indicating that high conformational sampling could be conducive to tropoelastins interactions between cell-surface receptors and elastic fiber-associated proteins. A new amino acid from hydrolysates of elastin. Elastagen is creating injectables using recombinant human tropelastin, a substance that's crucial for producing elastin fibers in the skin. N. Y. Acad. 29, 152159. Allergan markets a portfolio of leading brands and best-in-class products for the central nervous system, eye care, medical aesthetics and dermatology, gastroenterology, womens health, urology and anti-infectivetherapeutic categories. A novel cell adhesion region in tropoelastin mediates attachment to integrin alphaVbeta5. Nat. Bochicchio, B., Yeo, G. C., Lee, P., Emul, D., Pepe, A., Laezza, A., et al. This phenomenon is supported by in vitro peptide studies, which note that increasing the space between PG motifs or removing prolines results in more ordered structures (Rauscher et al., 2006). Unlike other companies that use paid endorsements and questionable data, NULASTIN science is proven by 3rd party clinical evaluation. Allergan's Acquisition of Elastagen - Global Legal Chronicle Dermatol. Identification of an elastin cross-linking domain that joins three peptide chains. Elastin - an overview | ScienceDirect Topics doi: 10.1073/pnas.1701877114, Reichheld, S. E., Muiznieks, L. D., Lu, R., Sharpe, S., and Keeley, F. W. (2019). Res. 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). Scientists find way to heal scars left behind by heart attacks It has become increasingly evident that tropoelastins sequence, structure and subsequent functionality are in a delicate balance; thus, perturbations to tropoelastins sequence can have far-reaching consequences for self-assembly and the resultant architecture of elastic fibers. Proc. doi: 10.1172/jci115204, Sherratt, M., Wess, T. J., Baldock, C., Ashworth, J., Purslow, P., Shuttleworth, C., et al. Allergan Snaps Up Sydney Biotech for Upfront Payment of US $95M 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). doi: 10.1080/07391102.1992.10508661, Tamburro, A. M., Pepe, A., and Bochicchio, B. (2020). 21:063001. doi: 10.1088/0965-0393/21/6/063001, Tarakanova, A., Huang, W., Weiss, A. S., Kaplan, D. L., and Buehler, M. J. The prevention of early self-aggregation in vitro is thought to be mediated by chaperone proteins (Hinek and Rabinovitch, 1994; Miao et al., 2013). doi: 10.1038/nrm3904, Bressan, G. M., Castellani, I., Giro, M. G., Volpin, D., Fornieri, C., and Pasquali Ronchetti, I. Colloid Interface Sci. The liquid structure of elastin. 280, 4093940947. 43, 131138. 3, 4 Elastin has a very low rate of turnover, so it . (2006). doi: 10.1016/j.str.2006.09.008, Rauscher, S., and Pomes, R. (2017). 396, 870873. 67-kD elastin-binding protein is a protective companion of extracellular insoluble elastin and intracellular tropoelastin. Patient Homepage | Accredo Biopolymers 20, 12471260. 3, 28322844. 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). J. Hum. How to Get LONGER Eyelashes - Guaranteed | NULASTIN (2007). (1983). 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). 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). Biopolymers 107:e23007. The ELN gene provides instructions for making a protein called tropoelastin. Biochemistry 45, 95189530. The most crucial of these properties is the ability to undergo many stretch-recoil cycles whilst maintaining the structural and functional integrity of elastic tissues over an organisms lifetime. The narrow specificity to v3 and 53 may also be beneficial compared with other ECM adhesion molecules such as fibronectin (which can adhere to up to 20 types of integrin) which may compete with and modulate binding to tropoelastin, and deliver opposing effects on cell proliferation. Biopolymers 103, 563573. Furthermore, the SAXS/SANS structure has been mapped to an elastic network model with tunable stiffness to probe the role of tropoelastins flexibility in fiber assembly (Yeo et al., 2016). (2015). (2017). 289, 14671477. To get started with texting, you will need: Your phone number The bifunctional cross-links can undergo further condensation to form tetrafunctional desmosine or isodesmosine (Partridge, 1966). Acad. The hydrophobic domains have been extensively studied and are responsible for facilitating tropoelastins ability to self-assemble (Vrhovski et al., 1997; Toonkool et al., 2001). Biopolymers [Epub ahead of print]. Natl. eLife 6:e26526. Matrix Biol. doi: 10.1016/j.biomaterials.2017.01.041, Tarakanova, A., Ozsvar, J., Weiss, A. S., and Buehler, M. J. FEBS J. Sequences and domain structures of mammalian, avian, amphibian and teleost tropoelastins: clues to the evolutionary history of elastins. 15, 786801. Acta Histochem. They are ubiquitous across most vertebrates other than lower vertebrates such as species from the superclass Agnatha (jawless fish) (Debelle and Tamburro, 1999). After a period of collaboration with the Elastagen team, US biopharmaceutical giant Allergan acquired Elastagen in 2018 for over $350 million in total deal value. (2008). 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 reflects the experimentally observed heterogeneity of cross-links in mature elastin, again giving weight to the hypothesis that the flexibility of tropoelastin is imperative for assembly (Schrader et al., 2018; Tarakanova et al., 2019a). doi: 10.1371/journal.pone.0046130, Hedtke, T., Schrader, C. U., Heinz, A., Hoehenwarter, W., Brinckmann, J., Groth, T., et al. Genet. Phase behavior and self-assembly of perfectly sequence-defined and monodisperse multiblock copolypeptides. (1988). 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. 84, 6880. Elastin makes up the majority of elastic fibers and is formed by the hierarchical assembly of its monomer, tropoelastin. J. Struct. Tropoelastin is a unique protein with biochemical and physical properties that allow it to rapidly self-assemble into fibrous structures. Exp. 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. Elastagens revolutionary technology is based on recombinant human tropoelastin, the precursor of elastin which is a key component of youthful skin. Coacervation characteristics of recombinant human tropoelastin. Biophys. 25, 492504. 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). Coacervation of tropoelastin. Mater. Variations in the relative abundance of alternatively spliced ELN mRNA transcripts have been observed between tissues, and this diversity is thought to be necessary for the fine tuning of the mechanical characteristics of tissues to suit their unique functional requirements (Reichheld et al., 2019). This deduction has been corroborated by the observation that tropoelastin with multiple allysine modifications displays conformational sampling comparable to that of the wild-type molecule, suggesting it is more likely to readily participate in self-assembly. Acta Gen. Subj. Front. Mater. 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. Caterpillar | Caterpillar to Relocate Global Headquarters to Dallas The evolutionary background and functional consequences of the rs2071307 polymorphism in human tropoelastin. 26, 17001709. Similar to other ECM proteins, such as collagen, tropoelastin covalently cross-links via its lysines. Earnings, adjusted for non-recurring costs, came . Computational smart polymer design based on elastin protein mutability. Biomacromolecules 18, 599609. J. doi: 10.1074/jbc.M113.518381, Lee, P., Yeo, G. C., and Weiss, A. S. (2017). Future investigations will allow the bridging of the gap between mesoscale simulations and microscopically observed coacervation (Clarke et al., 2006). ELN gene: MedlinePlus Genetics (2005). Chem. Tropoelastin is the soluble precursor of elastin that is secreted as a 60-70-kDa monomer by elastogenic cells such as fibroblasts, lung alveolar cells, chondrocytes, and vascular SMCs [16]. Baul, U., Bley, M., and Dzubiella, J. Dyn. 284, 22162230. Med. Molecular model for elastin structure and function. Elastin and other dermal components are gradually lost through aging, sun damage, and following injury, highlighting a need to replace these components to repair the skin. Powered by Madgex Job Board Software. Cell Biol. Lysyl oxidase-like 2 (LOXL2)-mediated cross-linking of tropoelastin. Importantly, the presence of fibrils indicates that the nanostructures formed during initial assembly contribute to the supramolecular structures that arise during both early (spherule) and later (fibril) stages of elastogenesis. Hogan Lovells represented Elastagen Pty Ltd. on the deal. Shape of tropoelastin, the highly extensible protein that - PNAS doi: 10.1021/bi034837t, Tamburro, A. M., Guantieri, V., and Gordini, D. D. (1992). 4, 508524. Elastin: Structure, Function, Skin Care & Supplements - Cleveland Clinic Natl. doi: 10.1021/bi00835a021, Gray, W. R., Sandberg, L. B., and Foster, J. The majority of tropoelastin synthesis occurs during perinatal development (Myers et al., 1983; Noguchi et al., 1990), however, synthesis may be triggered in response to tissue damage (Parks et al., 1992) or during diseases such as atherosclerosis (Phinikaridou et al., 2018). Acad. Sci. J. Biol. (2020). 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. Human tropoelastin improves rat heart function postmyocardial infarction and could potentially be used to treat heart failure. 624, 137146. Matrix Biol. Reichheld, S. E., Muiznieks, L. D., Keeley, F. W., and Sharpe, S. (2017). Studies on the reduction of elastin. Clinical Relevance of Elastin in the Structure and Function of Skin 260, 32553258. Tropoelastin #5052. doi: 10.1046/j.1432-1327.1999.00891.x, Yamauchi, Y., Tsuruga, E., Nakashima, K., Sawa, Y., and Ishikawa, H. (2010). The smooth muscle cell. Developmental changes of tropoelastin synthesis by rat pulmonary fibroblasts and effects of dexamethasone. Effect of peptide sequence on the LCST-like transition of elastin-like peptides and elastin-like peptidecollagen-like peptide conjugates: simulations and experiments. Bonnans, C., Chou, J., and Werb, Z. Modulation by elastin peptide VGVAPG of cell proliferation and elastin expression in human skin fibroblasts. Biomaterials 127, 4960. Molecular dynamics modeling of aggregating tropoelastin-derived peptide chains points to the maintenance of a hydrated, disordered, liquid-like state due to the formation of short-lived inter-chain bonds (Rauscher and Pomes, 2017; Reichheld et al., 2020), mostly likely due to the inducement of random coils by PG repeats (vide supra). 87, 18281834. Res. Tropoelastins domains each arise from single exons of the ELN gene. J. Biochem. Biochemistry 36, 84138421. Below the coil is a flexible hinge region made up of domains 2024, which are directly adjacent to the bridge regions of domains 2526. Crucially, these simulations revealed that self-assembly starts with a nucleation event and elongation proceeds via both globular and fibrillar structures (Tarakanova et al., 2019a).