Liquid State of (Elastomeric) ProteinsWhen: Thursday, March 14, 2013 at 4:00 pm
Where: DA 114
Speaker: Régis Pomès
Organization: Senior Scientist, Molecular Struture and Function, Hospital for Sick Children, Associate Professor, Department of Biochemistry, University of Toronto
Sponsor: Physics Colloquium
Self-assembled elastomeric proteins make up a highly-unusual class of structural proteins which are responsible for the elastic properties of biological tissues as diverse as spider silks and lung alveoli. In humans, elastin is the polymeric extracellular matrix protein responsible for extensibility and elastic recoil in lungs, skin, and large blood vessels. Although the self-organization and mechanical properties of elastin have spurred interest in this protein as a model for useful biomimetic polymers, such as vascular grafts or artificial skin, the molecular determinants of these properties are poorly understood. We use molecular dynamics simulations to examine the structural and thermodynamic basis for the self-assembly and mechanical properties of elastin-like polypeptides.
Our results indicate that an essential property of self-assembled elastomeric proteins is to remain disordered even in the aggregated state, with structural disorder serving at once to avoid misfolding into rigid amyloid aggregates (the prevalent form of protein assemblies) and to drive elastic recoil. Furthermore, massive sampling in explicit solvent provides an ensemble description of phase-separated peptide aggregates in which the polypeptide chains exhibit liquid-like properties characteristic of a polymer melt. Together, our findings reconcile key features of seemingly-contradictory structural models spanning 70 years of elastin research and support a unified model of protein aggregates in which hydration and conformational disorder are fundamental requirements for elastomeric function.