doi: 10.1016/j.bbrc.2010.05.013, Elvin, C. M., Carr, A. G., Huson, M. G., Maxwell, J. M., Pearson, R. D., Vuocolo, T., et al. 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). doi: 10.1074/jbc.M507309200, Brown-Augsburger, P., Tisdale, C., Broekelmann, T., Sloan, C., and Mecham, R. P. (1995). (2017). Cytochem. Our understanding of key aspects of the assembly process have been unclear due to the intrinsic properties of elastin and tropoelastin that render them difficult to study. Acad. Computational models have also been leveraged to pinpoint the molecular consequences of synthetic and disease mutations of tropoelastin. 25, 10231029. Thus, elastin is responsible, in great part, for the properties of elastic fibers. Nature 437, 9991002. The elastin receptor complex: a unique matricellular receptor with high anti-tumoral potential. Tropoelastin #5052. The resultant bending motion rather than scissors-twist motion that stemmed from this stabilization highlights the mutants diminished flexibility as a key driver of impaired fiber assembly in cutis laxa (Tarakanova et al., 2018). Biochemistry 36, 84138421. The understanding of tropoelastins structure has been hindered by numerous intrinsic properties of the molecule. Cellular activities are mediated through interactions between tropoelastin or EDPs and specific receptors on the cell surface. Engineering a highly elastic human protein-based sealant for surgical applications. Res. Studies on the reduction of elastin. doi: 10.1021/acs.biomac.6b01759, Mackay, J. P., Muiznieks, L. D., Toonkool, P., and Weiss, A. S. (2005). (2020). (2019a). 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). doi: 10.1267/ahc.10026, Yang, A. S., and Honig, B. The self-assembly properties and nanostructure of these extra teleost isoforms are yet to be investigated. Tropoelastin is secreted as a 6070 kDa protein to the cell surface where it participates in self-assembly (Hinek and Rabinovitch, 1994; Figure 3). doi: 10.1006/jmbi.1995.0502, Yeo, G. C., Baldock, C., Tuukkanen, A., Roessle, M., Dyksterhuis, L. B., Wise, S. G., et al. Biomacromolecules 18, 599609. doi: 10.1016/j.ajhg.2009.09.013. This temperature is also known as the transition temperature. Codistribution analysis of elastin and related fibrillar proteins in early vertebrate development. J. Biol. Sequences and domain structures of mammalian, avian, amphibian and teleost tropoelastins: clues to the evolutionary history of elastins. 276, 3603536042. doi: 10.1016/j.actbio.2013.08.003, Wu, W. J., and Weiss, A. S. (1999). Biochemistry 37, 1461314622. Tropoelastins hydrophobic domains are primarily responsible for facilitating coacervation (Tamburro et al., 1992; Miao et al., 2003; Muiznieks et al., 2003). FASEB J. KP domains are found closer toward the N-terminus, whereas KA domains are closer to the C-terminus and include alanine tracts (Indik et al., 1987). 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. Self-healing and thermoreversible rubber from supramolecular assembly. Elastagens revolutionary recombinant human tropoelastin, is identical to that present in human tissue and has many clinical applications, including effective breakthrough treatments for acne scars, stretch marks, aesthetic skin repair and wound repair. 85, 593605. Sci. J. Med. Res. 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). It's a major component of tissues in your body that require stretchiness, like your lungs, bladder, large blood vessels and some ligaments. Reichheld, S. E., Muiznieks, L. D., Huynh, Q., Wang, N., Ing, C., Miao, M., et al. Res. Chem. A., and Rucker, R. B. Sci. 260, 32553258. Hydrophobic domains of human tropoelastin interact in a context-dependent manner. Med. Similarly, a mutation model associated with cutis laxa, or loose skin disease (Hu et al., 2006), was found to exhibit higher stability compared with the wild-type molecule due to the increased longevity of its salt bridges (Hu et al., 2006; Tarakanova et al., 2018). 26, 125135. 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. Nature 246, 461466. 278, 1849118498. Biophys. 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). doi: 10.1016/j.matbio.2009.10.003, Tu, Y., Wise, S. G., and Weiss, A. S. (2010). J. Mol. Am. Tropoelastin. (2021). doi: 10.1016/j.jmb.2020.08.023, Luan, C. H., Harris, R., Prasad, K. U., and Urry, D. W. (1990). Sci. Injectable biomaterial compositions formed from tropoelastin for tissue repair and restoration. Developmental changes of tropoelastin synthesis by rat pulmonary fibroblasts and effects of dexamethasone. I thank my team at the University of Sydney and greatly look forward to seeing our science commercialized by Allergan.. Bull. This process is reversible and thermodynamically controlled and does not require protein cleavage. 396, 870873. doi: 10.1248/bpb.b13-00933, Ozsvar, J., Tarakanova, A., Wang, R., Buehler, M. J., and Weiss, A. S. (2019). (2012). 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. Invest. Free energy determinants of secondary structure formation: I. alpha-Helices. Instead, tropoelastin domains 1418 and 36 (RKRK sequence) have been found to bind to both integrins. Upon secretion tropoelastin has the propensity to self-aggregate through a process known as coacervation. AW gratefully acknowledges NHMRC funding (Ref: 1195827). The first successful experiments to define the 3D envelope of tropoelastin utilized small angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS) (Baldock et al., 2011). Tropoelastin has a defined shape in solution but paradoxically also displays a large percentage of flexible, disordered regions needed for molecular elasticity (4, 5).The tertiary structure of human tropoelastin represents an ensemble of elastic conformers (3, 6), yet occasional conserved sequence elements hint at requirements for functional demands in one or more key parts of this molecule (7 . Elastic fibers are eventually formed after extensive cross-linking through a process termed maturation (Yeo et al., 2016). 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). Elastogenesis occurs during replacement fibrosis in human heart disease and can be accelerated in vitro via tropoelastin treatment. (2013). J. Biol. Tropoelastin interacts with microfibril components including fibrillin-1, fibulin-4, and -5, and other associated molecules such as latent transforming growth factor binding protein-4 (Visconti et al., 2003; McLaughlin et al., 2006; Urban et al., 2009; Yamauchi et al., 2010; Noda et al., 2013; Lockhart-Cairns et al., 2020). Structure of the elastin gene and alternative splicing of elastin mRNA: implications for human disease. 34, 8190. Biopolymers 107:e23007. 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). Pharmacol. Tropoelastin is frequently described in the literature as an unstructured protein, mainly because models of elasticity invoke an element of disorder within the structure (4, 9, 10).While this concept appears to be the case at the fine, more subtle intramolecular level, chaos alone is unlikely to explain the ordered assembly of tropoelastin which culminates in the formation of organized . Biochim. Matrix Biol. Transient tropoelastin nanoparticles are early-stage intermediates in the coacervation of human tropoelastin whose aggregation is facilitated by heparan sulfate and heparin decasaccharides. Direct observation of structure and dynamics during phase separation of an elastomeric protein. 167, 94103. Biochemistry 52, 77317741. Sci. III. [Epub ahead of print]. Biol. Coacervation involves the agglomeration of protein molecules, which is an . doi: 10.1002/bip.1981.360200611. The business could generate net sales of approximately $7 to $8 billion in 2025 from $3.8 billion in 2017. Implications for microfibril and elastic fiber assembly. Tropoelastin, the soluble precursor to elastin, and the degradation products of fragmented elastic fibers also have important chemical signaling properties. 10, 15321541. The importance of tropoelastins flexibility during self-assembly has also been examined in the light of natural allysine modifications, which condense to give cross-links within mature elastin (discussed further in the following section) (Ozsvar et al., 2019). Coacervation characteristics of recombinant human tropoelastin. doi: 10.1128/mcb.26.5.1700-1709.2006, Mecham, R. P. (1991). Mater. Chem. doi: 10.1021/bi0610092, Cordier, P., Tournilhac, F., Souli-Ziakovic, C., and Leibler, L. (2008). 280, 4093940947. Sci. Tropoelastin: a novel marker for plaque progression and instability. 249, 997998. Background: Elastin is an essential component of the dermis, providing skin with elasticity and integrity. Fibrillin-1 and -2 also interact with proteoglycans (Tiedemann et al., 2001), which coupled with tropoelastin/GAG interactions provide a pathway to the formation of elastic fibers. 432, 57365751. 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. Form. Cross-linking domains are capable of modulating self-assembly when incorporated into peptides and biomaterials derived from tropoelastins hydrophobic domains. 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). 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). (2011). Further to this, the flexibility of the hydrophobic domains may also play a key role in self-assembly. Elastagen's revolutionary recombinant human tropoelastin, is identical to that present in human tissue and has many clinical applications, including effective breakthrough treatments for acne. Chem. 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). Matrix Biol. Microfibrils comprise multiple proteins, of which fibrillin-1 is the most common. doi: 10.1016/0014-4800(65)90015-8, He, D., Chung, M., Chan, E., Alleyne, T., Ha, K. C. H., Miao, M., et al. 31, 261272. Exp. Biochemistry 42, 1334713362. The computational model uncovered the contributions of each molecular region to the flexibility of the molecule. Glycosaminoglycans (GAGs) are negatively charged, linear polysaccharides, which can be either sulfated [heparan sulfate (HS) or chondroitin sulfate] or non-sulfated (hyaluronic acid). 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. Tropoelastins sequence and domain arrangement. J. Mol. Partridge, S. M. (1966). Figure 3. 1862, 324334. Coarse-grained model of tropoelastin self-assembly into nascent fibrils. Pathol. Characterization of the complete human elastin gene. Chem. 120, 419426. J. EBP plays two roles in the assembly of elastin. Nat. 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). . 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. doi: 10.1002/jcp.20546, Kozel, B. In vitro elastogenesis: instructing human vascular smooth muscle cells to generate an elastic fiber-containing extracellular matrix scaffold. Transglutaminase-mediated cross-linking of tropoelastin to fibrillin stabilises the elastin precursor prior to elastic fibre assembly. U.S.A. 115, 73387343. doi: 10.1016/j.jsb.2005.02.005, Martin, S. L., Vrhovski, B., and Weiss, A. S. (1995). The N-terminal head caps an extended coil region that consists of domains 218. J. Biol. Bioeng. Positively charged lysine residues in domains 17 were identified to interact with negatively charged HS, most likely via ionic interactions (Lee et al., 2017). Biomacromolecules 20, 11781189. doi: 10.1007/s004030050227, Tamburro, A. M., Bochicchio, B., and Pepe, A. To get started with texting, you will need: Your phone number Sci. Biopolymers 103, 563573. Natl. 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. 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. Fluor: Q4 Earnings Snapshot. (2005). doi: 10.1074/jbc.M113.533893, Reiersen, H., and Rees, A. R. (2000). J. Adv. Computational approaches have gained popularity in recent decades as their methodologies have been refined to provide accurate atomistic scale insights into molecular structure and movement (Tarakanova et al., 2018). Biomaterials 127, 4960. Biosci. Elastin is one of the most abundant proteins in your body. Arch. 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). 1, 2 Elastogenesis, the process of elastin formation, mainly occurs during the fetal and early neonatal development of organs such as blood vessels, lungs, and skin. Elastic fibers are present in the extracellular matrix (ECM) of vertebrate tissues, such as the skin, lungs, cardiovascular system, cartilage, and tendons. Tropoelastins domains each arise from single exons of the ELN gene. PLoS One 7:e46130. doi: 10.1021/bi034837t, Tamburro, A. M., Guantieri, V., and Gordini, D. D. (1992). 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). Elastin binding protein (EBP) is a splice variant of -galactosidase, that recognizes the repetitive hydrophobic sequences (VGVAPG) of tropoelastin (Tajima et al., 1997). Chem. 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). 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). 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). Elastagen is an exciting clinical-stage company with an advanced tissue repair platform based on tropoelastin. 252, 351365. 26, 17001709. Completion of the transition is subject to customary closing conditions, including review by Australias Foreign Investment Review Board. doi: 10.1046/j.1432-1327.1998.2580001.x, Wang, Z., Liu, L., Mithieux, S. M., and Weiss, A. S. (2020). Proc. The elastin receptor complex transduces signals through the catalytic activity of its Neu-1 subunit. 9:643110. doi: 10.3389/fbioe.2021.643110. Tropoelastins C-terminal domain 36 (yellow) does not fall into either category as it contains a distinct sequence capped with a Gly-Arg-Lys-Arg-Lys (GRKRK) motif and is primarily involved in cell interactions. doi: 10.1371/journal.pone.0046130, Hedtke, T., Schrader, C. U., Heinz, A., Hoehenwarter, W., Brinckmann, J., Groth, T., et al. Crosslinking [ edit] Proc. Reichheld, S. E., Muiznieks, L. D., Keeley, F. W., and Sharpe, S. (2017). Domain 36 of tropoelastin in elastic fiber formation. (2016). Co-author Professor Anthony Weiss from the Charles Perkins Centre and Faculty of Science explained: "Tropoelastin can repair the heart because it is a precise replica of the body's natural elastic protein,". 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). Stages in tropoelastin coalescence during synthetic elastin hydrogel formation. FEBS J. Tropoelastin is a unique protein with biochemical and physical properties that allow it to rapidly self-assemble into fibrous structures. J. Biochem. doi: 10.1002/bip.360291403, Luo, P., and Baldwin, R. L. (1997). A comprehensive map of human elastin cross-linking during elastogenesis. Elastin is the major component of elastic fibers, which are a major component of the tissue that supports the body's joints . Calorim. Proline and glycine control protein self-organization into elastomeric or amyloid fibrils. Single nucleotide polymorphisms and domain/splice variants modulate assembly and elastomeric properties of human elastin. Multimers may undergo further transitions, such as branching, to form spherules made of multimer aggregates (Tu et al., 2010). Colloid Interface Sci. Domains 17-27 of tropoelastin contain key regions of contact for coacervation and contain an unusual turn-containing crosslinking domain. Exon 26-coded polypeptide: an isolated hydrophobic domain of human tropoelastin able to self-assemble in vitro. Tropoelastins amino acid sequence predominantly consists of non-polar residues including glycine, valine, alanine, and proline (Debelle and Tamburro, 1999). Micron 41, 268272. U.S.A. 112, E4408E4415. (2007). J. Cell Physiol. Proline-poor hydrophobic domains modulate the assembly and material properties of polymeric elastin. 264, 88878891. doi: 10.1007/978-1-4684-9093-0_25, Scandolera, A., Odoul, L., Salesse, S., Guillot, A., Blaise, S., Kawecki, C., et al. 28, 432441. doi: 10.1002/ajmg.1320340115, Indik, Z., Yeh, H., Ornstein-Goldstein, N., Sheppard, P., Anderson, N., Rosenbloom, J. C., et al. doi: 10.1074/jbc.M113.518381, Lee, P., Yeo, G. C., and Weiss, A. S. (2017). A., Ishibashi, H., Werneck, C. C., Keeley, F. W., Zhang, L., et al. Structure 14, 16671676. Cell Biol. doi: 10.1002/chem.200305661. Biol. doi: 10.1016/j.matbio.2008.02.006, Phinikaridou, A., Lacerda, S., Lavin, B., Andia, M. E., Smith, A., Saha, P., et al. doi: 10.1038/246461a0, Haust, M. D., More, R. H., Bencosme, S. A., and Balis, J. U. Tropoelastin is a precursor protein of elastin, and is composed of hydrophilic (lysine, valine and proline) and hydrophobic (glycine, valine and proline) domains. 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. Biochim. Int. Cryo-electron microscopy is a rapidly developing method and likely to contribute to structural knowledge of tropoelastin. Lab. 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. Closer to the base of the molecule, the flexible hinge region between domains 21 and 23 presented with a scissors-like bending, which is now believed to contribute to elasticity and multimeric assembly through enhanced conformational space sampling (Tarakanova et al., 2019b). Eur. For Elastagen contact: Robert Daniels, CEO +61 2 9209 4054. 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). Acta Histochem. J. Biol. "We believe it's in the best strategic interest of the company to make this move, which supports Caterpillar's strategy for profitable . Elastin is heterogeneously cross-linked. Four days after a heart attack, purified tropoelastin was injected into the heart. Figure 2. This content is for members only. Acad. Sci. Initially, in vitro coacervation is characterized by the rapid aggregation of tropoelastin. Elastagen's revolutionary recombinant human tropoelastin, is identical to that present in human tissue and has many clinical applications, including effective breakthrough treatments for acne scars, stretch marks, aesthetic skin repair and wound repair. A., Torres, A. R., Alvarez, V. L., and Janata, J. Arch. Shape of tropoelastin, the highly extensible protein that controls human tissue elasticity. 250, 9298. U.S.A. 116, 20422051. Simul. Matrix Biol. Stages of hierarchical assembly of elastic fibers. Cardiovasc. Front. In contrast, higher temperatures allow the breaking of the hydrogen bonds of the ordered water, dissipating the clathrate shells and permitting the association of the hydrophobic domains (Yeo et al., 2011). 67-kD elastin-binding protein is a protective companion of extracellular insoluble elastin and intracellular tropoelastin. doi: 10.1073/pnas.1701877114, Reichheld, S. E., Muiznieks, L. D., Lu, R., Sharpe, S., and Keeley, F. W. (2019). The bifunctional cross-links can undergo further condensation to form tetrafunctional desmosine or isodesmosine (Partridge, 1966). In addition to the RKRK sequence, domain 36 contains tropoelastins sole two cysteines and only disulfide bond. Homology models for domains 21-23 of human tropoelastin shed light on lysine crosslinking. In order to eliminate this limitation, human tropoelastin has been expressed in a recombinant bacterial system and the protein has been highly purified. Non-polar residues are a major contributor to protein folding, as their unfavorable interactions with water drive them to bury into the protein core, however, as tropoelastin is comprised of numerous hydrophobic domains, it has been demonstrated that many of these domains will be at least partially solvent exposed (Dyksterhuis et al., 2007). 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. Differential expression of two tropoelastin genes in zebrafish. Similar to other ECM proteins, such as collagen, tropoelastin covalently cross-links via its lysines. Biophys. Elastagen Pty Ltd, a clinical stage company developing medical device products based on recombinant tropoelastin, today announced. Cell Biol. Elastin is highly hydrophobic, extensively cross-linked, and is assembled into elastic fibers in a dynamic process involving cells, cell surface receptors, and numerous elastic fiber . 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. Elastases can be in the form of serine- (e.g., Ela-2), cysteine- (e.g., cathepsin I), or matrix metalloproteinases (MMP-2, -7, -9, and -12), and bioactive peptides include the VGVAPG peptide. doi: 10.1096/fj.201801860RR, Schrader, C. U., Heinz, A., Majovsky, P., Karaman Mayack, B., Brinckmann, J., Sippl, W., et al. Rep. 8, 116. Med. Biophys. A., Wachi, H., Davis, E. C., and Mecham, R. P. (2003). Model. 293, 1510715119. Pepe, A., Flamia, R., Guerra, D., Quaglino, D., Bochicchio, B., Pasquali Ronchetti, I., et al. Commun. HS, which is present on cell surface proteoglycans (syndecans and glypicans), interacts strongly with tropoelastin (Cain et al., 2005). Intracellularly, EBP is associated with tropoelastin after the release of the signal peptide and acts as a chaperone to prevent self-aggregation and proteolysis as it transported to the cell membrane, after which EBP is then recycled and serves as a reusable shuttle protein (Hinek et al., 1995). 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). 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). J. Biol. Acta 303, 363369. A cell adhesive peptide from tropoelastin promotes sequential cell attachment and spreading via distinct receptors. Developing elastic tissue. J. Biochem. Tropoelastin is typically used as a thin coating on tissue culture surfaces. 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). 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). Allergan's Acquisition of Elastagen. doi: 10.1016/0304-4165(83)90357-4, Narayanan, A. S., Sandberg, L. B., Ross, R., and Layman, D. L. (1976). Biol. doi: 10.1093/protein/13.11.739, Roberts, S., Dzuricky, M., and Chilkoti, A. doi: 10.1073/pnas.1801205115, Tarakanova, A., Yeo, G. C., Baldock, C., Weiss, A. S., and Buehler, M. J. Biopolymers [Epub ahead of print]. Acad. eLife 6:e26526. Matrix Biol. For this injection, the researchers used a new . Total synthesis and expression in Escherichia coli of a gene encoding human tropoelastin. This canonical computational structure was determined to be highly similar to the envelope found via SAXS/SANS, where both consist of an extended molecular body accompanied by a protruding foot (Baldock et al., 2011). 84, 6880. Cooperativity between the hydrophobic and cross-linking domains of elastin. Elastagen's technology is based on human tropoelastin . Anal. 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).