Cell Physiol. Macromol. For Allergan, contact: Lisa Brown 1-862-261-7320, 1985 - 2023 BioSpace.com. 22, 109121. Background: Elastin is an essential component of the dermis, providing skin with elasticity and integrity. Fabricating organized elastin in vascular grafts. (2006). Sci. Although there is no 3D structure for porcine tropoelastin, porcine tropoelastin differs from that of humans (Sandberg et al., 1977), leaving it unclear as to whether these domains align as expected in human tissue. Eur. 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. 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. Matrix Biol. Fed. doi: 10.1073/pnas.1111615108, Yeo, G. C., Baldock, C., Wise, S. G., and Weiss, A. S. (2017). Elastin is heterogeneously cross-linked. Natl. 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. 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). Acad. Calorim. (2018). Natl. Lyophilized Powder. doi: 10.1083/jcb.68.3.411, Noda, K., Dabovic, B., Takagi, K., Inoue, T., Horiguchi, M., Hirai, M., et al. Natl. doi: 10.1128/mcb.26.5.1700-1709.2006, Mecham, R. P. (1991). Chem. Increased cyclic GMP levels lead to a stimulation of elastin production in ligament fibroblasts that is reversed by cyclic AMP. Targeted modulation of tropoelastin structure and assembly. Parameter, Testing, and Method. 10:034102. doi: 10.1088/1748-6041/10/3/034102, Hinek, A., Keeley, F. W., and Callahan, J. doi: 10.1038/nature04085. 150, 154162. 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). Studies on the reduction of elastin. 25, 492504. Front. Dyn. Weiss Lab Home Integrin alpha v beta 3 binds a unique non-RGD site near the C-terminus of human tropoelastin. CB gratefully acknowledges BBSRC funding (Ref: BB/R008221/1). Biochem. 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). 41, 494497. Allergan Highlights Key Growth Drivers for Medical Aesthetics - PR Newswire 410, 317323. The tropoelastin that Elastagen manufactures is an identical copy of what naturally occurs in human tissue, meaning the clinical application opportunities for this has tremendous potential . 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. We are making enrolling in text alerts easier than ever. 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). Tropoelastin is the building block of elastin, a key component of the skin, arteries and lungs that gives tissue its elasticity. J. Clin. doi: 10.1016/j.matbio.2009.10.003, Tu, Y., Wise, S. G., and Weiss, A. S. (2010). Its hydrophobic (pink) and cross-linking (blue) domains consist of repetitive motifs that contribute uniquely to elastin assembly. (1989). Further to this, the current model of elastin assembly does not account for how long strings or sheets of tropoelastin are capable of forming spherules on a macroscopic scale (Tu et al., 2010). Cryo-electron microscopy for structural analysis of dynamic biological macromolecules. 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. doi: 10.1267/ahc.10026, Yang, A. S., and Honig, B. J. Bashir, M. M., Indik, Z., Yeh, H., Ornstein-Goldstein, N., Rosenbloom, J. C., Abrams, W., et al. Elastins subunit, tropoelastin, is a soluble 6070 kDa protein which has been intensely studied over the past three decades. Mater. Most organisms contain one copy of ELN, other than teleosts and amphibians which notably possess two distinct types of ELN genes (He et al., 2007; Miao et al., 2007, 2009). The first is an intracellular role as a tropoelastin chaperone and the second is as part of the elastin receptor complex (ERC). (2020). U.S.A. 108, 43224327. Polymorphisms in the human tropoelastin gene modify in vitro self-assembly and mechanical properties of elastin-like polypeptides. Nature 451, 977980. Its estimated half-life of 70 years (Shapiro et al., 1991) is due to its extensive cross-linking and high hydrophobicity, which render it resistant to degradation (Vrhovski and Weiss, 1998; Schrader et al., 2018; Hedtke et al., 2019). 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). Targeted disruption of fibulin-4 abolishes elastogenesis and causes perinatal lethality in mice. In vitro elastogenesis: instructing human vascular smooth muscle cells to generate an elastic fiber-containing extracellular matrix scaffold. 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). Coarse-grained model of tropoelastin self-assembly into nascent fibrils. February 14, 2018 Michael Patrini. Injectable biomaterial compositions formed from tropoelastin for tissue repair and restoration. Matrix Biol. It's a stretchy protein that resembles a rubber band it can stretch out (extend) and shrink back (recoil). 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. Free energy determinants of secondary structure formation: I. alpha-Helices. 1862, 324334. Chem. Acad. 149, 282289. J. Biol. J. Biomol. Matrix Biol. doi: 10.1074/jbc.M113.518381, Lee, P., Yeo, G. C., and Weiss, A. S. (2017). Chem. (2005). II. Tropoelastin, the soluble precursor to elastin, and the degradation products of fragmented elastic fibers also have important chemical signaling properties. 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. doi: 10.1016/j.actbio.2013.08.003, Wu, W. J., and Weiss, A. S. (1999). Genet. Elastogenesis is the term that collectively describes the hierarchical process of elastic fiber formation, and is comprised of distinct phases: tropoelastin synthesis, coacervation, cross-linking, and deposition. Biochem. Thus, elastin is responsible, in great part, for the properties of elastic fibers. Biopolymers 20, 12471260. More recently, the computational model of tropoelastin has been leveraged to characterize higher-order structures and probe self-assembly (Tarakanova et al., 2019a). 16,17 We have previously shown that monomeric TE is utilized as a substrate by dermal fibroblasts in the formation of elastin fibroblasts in vitro, where All authors contributed to writing and editing the review. Structure of the elastin gene and alternative splicing of elastin mRNA: implications for human disease. doi: 10.1006/jmbi.2000.3901, Baldock, C., Oberhauser, A. F., Ma, L., Lammie, D., Siegler, V., Mithieux, S. M., et al. The next stage of elastin assembly involves the deposition of tropoelastin spherules onto the microfibril scaffold of elastic fibers. Cytochem. Copyright 2021 Ozsvar, Yang, Cain, Baldock, Tarakanova and Weiss. Biochemistry 36, 84138421. Mechanism of helix induction by trifluoroethanol: a framework for extrapolating the helix-forming properties of peptides from trifluoroethanol/water mixtures back to water. On a per-share basis, the Irving, Texas-based company said it had profit of 1 cent. doi: 10.1007/978-3-319-71530-8_13-1, Wen, Q., Mithieux, S. M., and Weiss, A. S. (2020). J. Biol. Hailed as a giant leap forward in hair rejuvenation, NULASTIN transforms the look of eyelashes up to 120% thicker and 61% longer. Chem. Crosslinking [ edit] This process is reversible and thermodynamically controlled and does not require protein cleavage. doi: 10.1016/j.tibtech.2019.08.005, Wise, S. G., and Weiss, A. S. (2009). Hogan Lovells represented Elastagen Pty Ltd. on the deal. In order to eliminate this limitation, human tropoelastin has been expressed in a recombinant bacterial system and the protein has been highly purified. Protein Eng. J. Hum. doi: 10.1016/j.jsb.2005.02.005, Martin, S. L., Vrhovski, B., and Weiss, A. S. (1995). 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). Tropoelastin is a low complexity protein on both primary and secondary sequence levels. (2017). Tropoelastin | Circulation: Cardiovascular Imaging Structure 14, 16671676. doi: 10.1074/jbc.M113.533893, Reiersen, H., and Rees, A. R. (2000). (2018). Allergan announced that it would be accessing Elastagen's next generation Juvederm dermal filler injectable portfolio, which will now also boast its "key 'youth protein' tropoelastin". doi: 10.1016/j.ajhg.2009.09.013. Institute of Polymers, Composites and Biomaterials, National Research Council (IPCB-CNR), Italy, Washington University in St. Louis, United States. Transglutaminase-mediated cross-linking of tropoelastin to fibrillin stabilises the elastin precursor prior to elastic fibre assembly. doi: 10.1021/bi00835a022, Lockhart-Cairns, M. P., Newandee, H., Thomson, J., Weiss, A. S., Baldock, C., and Tarakanova, A. Domains 12 to 16 of tropoelastin promote cell attachment and spreading 284, 22162230. 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. (2018). J. Biol. Further to this, the flexibility of the hydrophobic domains may also play a key role in self-assembly. 25, 10231029. Natl. (2005). The self-assembly properties and nanostructure of these extra teleost isoforms are yet to be investigated. Matrix Biol. Fluor: Q4 Earnings Snapshot | AP News Stiffness within the context of self-assembly has also been examined with both coarse grained and full-atomistic simulations using polypeptides derived from tropoelastins hydrophobic domains. doi: 10.1093/protein/13.11.739, Roberts, S., Dzuricky, M., and Chilkoti, A.