The Liquid State of (Elastomeric) Proteins

Abstract

Self-assembled elastomeric proteins make up an important and unusual class of structural proteins endowing biological tissues as diverse as spider silks and lung alveoli with extensibility and elastic recoil. In humans, elastin is the polymeric extracellular matrix protein responsible for the elasticity of lungs, skin, the bladder, the uterus, and large blood vessels. Elastin self-assembly involves a process of liquid-liquid phase separation called coacervation. Although the structure of elastin in the resulting matrix is unknown, the source of elastic recoil is known to be primarily entropic. Two different sources of entropy have been proposed in seemingly-contradictory models: rubber-like models attribute the elasticity of elastin to the entropy of the polypeptide chain in random-coil conformation, whereas “liquid drop” models ascribe the recoil of this highly-hydrophobic protein to the hydrophobic effect. Although its self-organization and mechanical properties have spurred interest in elastin as a model for useful biomimetic polymers, the molecular determinants of these properties are poorly understood.We use atomistic molecular dynamics simulations in explicit solvent to examine the structural basis for the self-assembly and mechanical properties of elastin-like polypeptides in water. Massive sampling over simulation times totalling 0.3 millisecond indicates that the peptides remain highly disordered (though not random) even in the aggregated state, and provides an ensemble description of phase-separated peptide aggregates in which the polypeptide chains exhibit liquid-like properties approaching those of a polymer melt. In this phase-separated state, the peptides are largely solvated by one another, although the polypeptide backbone remains significantly hydrated. Crucially, both conformational entropy and hydrophobic burial drive the formation of this protein-rich phase, which may be called the liquid state of proteins. These findings support a unified model of self-assembled elastomeric proteins in which these two entropic forces play essential roles in both self-assembly and elastic recoil.