Tropoelastin: A versatile, bioactive assembly module

Abstract

Elastin provides structural integrity, biological cues and persistent elasticity to a range of important tissues including the vasculature and lungs. Its critical importance to normal physiology makes it a desirable component of biomaterials that seek to repair or replace these tissues. The recent availability of large quantities of the highly purified elastin monomer, tropoelastin, have allowed for a thorough characterization of the mechanical and biological mechanisms underpinning the benefits of mature elastin. 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. Insights into the structure and behavior of tropoelastin have translated into increasingly sophisticated elastin-like biomaterials, evolving from classically manufactured hydrogels and fibers to new forms, stabilized in the absence of incorporated cross-linkers. Tropoelastin is also compatible with synthetic and natural co-polymers, expanding the applications of its potential use beyond traditional elastin-rich tissues and facilitating finer control of biomaterial properties and the design of next-generation tailored bioactive materials.

Perspectives on the Molecular and Biological Implications of Tropoelastin in Human Tissue Elasticity

“…[30] [31] Over the past few years, we and others have found that, in vitro, these molecules are not needed for the spatial and temporal elastin assembly of tropoelastin. [9,15,20,26,32,33] This may be due to the fact that elastin is over nine times more abundant than microfibrillar components, and therefore tropoelastin-tropoelastin interactions dominate. [34] The observed tropoelastin and aggregate structures are similar to those found in natural tissues, as evidenced by electron microscopy, which supports the concept of an aggregation unit corresponding to tropoelastin assemblies.…”

“…[37] By exploring the functional roles of domains by systematically introducing mutations at selected sites across tropoelastin, in concert with SAXS and allied methods including SANS, NMR, and molecular dynamics on these constructs, we have solved the solution structures for the normal and a panel of mutant forms of tropoelastin. [9,10,20,26] In each of the mutant cases, there is altered assembly. This has facilitated mapping of these effects onto specific parts of the molecule, together with comparison of the assembly performance of wild-type and mutant forms in vitro and in concert with elastogenic cells.…”

“…[23] In contrast to the complex assembly of collagen type I, which relies on multiple proteolytic processing steps of the associating heterotrimer units, [25] tropoelastin is more amenable to study because its unprocessed monomers assemble on the path to elastin. [26] Multiple laboratories [27,28,29] have elegantly explored how microfibrils contribute to the distribution of elastin in vivo and that low-abundance molecules such as fibulins are needed for elastic fibre organization in vivo. [30] [31] Over the past few years, we and others have found that, in vitro, these molecules are not needed for the spatial and temporal elastin assembly of tropoelastin.…”

Revascularization of decellularized lung scaffolds: principles and progress

“…Tropoelastin is the soluble precursor of the insoluble fibrillar elastin in situ (129). EN is an important protein that impacts lung development predominantly during the alveolar stage.…”

Tropoelastin Enhances Nitric Oxide Production by Endothelial Cells

“…This protein is particularly abundant in the vascular wall, being prominent in the aorta and also in elastic vessels. While cell signaling is directed by tropoelastin through cell-surface interactions [2], specific integrin binding sites have been recently identified in tropoelastin where they drive the attachment and proliferation of fibroblasts, endothelial and endothelial progenitor cells [3][4][5]. Also contained within the tropoelastin sequence are short repeating hydrophobic signaling motifs that are recognized by the elastin binding protein (EBP) and promote cellular chemotaxis and vasorelaxation [6].…”