title: Contribution of domain 30 of tropoelastin to elastic fiber formation and material elasticity.
abstract: Elastin is a fibrous structural protein of the extracellular matrix that provides reversible elastic recoil to vertebrate tissues such as arterial vessels, lung, and skin. The elastin monomer, tropoelastin, contains a large proportion of intrinsically disordered and flexible hydrophobic sequences that collectively are responsible for the initial phase separation of monomers during assembly, and are essential for driving elastic recoil. While structural disorder of hydrophobic sequences is controlled by a high proline and glycine residue composition, hydrophobic domain 30 of human tropoelastin is atypically proline-poor, and forms β-sheet amyloid-like fibrils as an individual peptide. We explored the contribution of confined regions of secondary structure at the location of domain 30 in human tropoelastin to fiber assembly and mechanical properties using a set of mutations designed to inhibit or enhance the propensity of β-sheet formation at this location. Our data support a dual role for confined β-sheet secondary structure in domain 30 of tropoelastin in guiding the formation of fibers, and as a determinant of stiffness and viscoelastic properties of cross-linked materials. Together, these results suggest a mechanism for specificity in fiber assembly, and elucidate structure-function relationships for the rational design of elastomeric biomaterials with defined mechanical properties.
authors.affiliation: Molecular Structure and Function Program, Hospital for Sick Children, 555 University Ave., Toronto, ON, M5G1X8, Canada.
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Muiznieks
authors.affiliation: Molecular Structure and Function Program, Hospital for Sick Children, 555 University Ave., Toronto, ON, M5G1X8, Canada.
authors.forename: Ming
authors.initials: M
authors.lastname: Miao
authors.affiliation: Molecular Structure and Function Program, Hospital for Sick Children, 555 University Ave., Toronto, ON, M5G1X8, Canada.
authors.forename: Eva E
authors.initials: EE
authors.lastname: Sitarz
authors.affiliation: Molecular Structure and Function Program, Hospital for Sick Children, 555 University Ave., Toronto, ON, M5G1X8, Canada.|Department of Biochemistry, 1 King's College Circle, University of Toronto, Toronto, ON, M5S1A8, Canada.|Department of Pathology and Laboratory Medicine, 1 King's College Circle, University of Toronto, Toronto, ON, M5S1A8, Canada.
authors.forename: Fred W
authors.initials: FW
authors.lastname: Keeley
mesh_terms: D000595:Amino Acid Sequence; D004548:Elasticity; D006801:Humans; D017433:Protein Structure, Secondary; D014333:Tropoelastin / Q000737:chemistry*
chemical_list: D014333:Tropoelastin
keywords: beta-sheet; biomaterial design; elastic fibers; elastin; entropic elasticity