Solvent Effects on the Conformational Equilibrium of Elastin-Like and Amyloidogenic Peptides

Abstract

The elasticity of many human tissues like skin, blood vessels, and lungs, is imparted by a self-assembling extracellular matrix protein called elastin. Elastin has received considerable interest due to the potential for developing new biomimetic materials. However, advances are impeded because the molecular basis for self-assembly and elastomeric properties are still largely unknown. Tropoelastin, the monomeric precursor of elastin, consists of alternating hydrophobic and cross-linking domains. Hydrophobic domains are responsible for self-aggregation. In a previous study, we have shown that the hydrophobic domains of elastin and of all other known self-assembling elastomeric proteins, such as spider silks and insect resilin, remain disordered even in the aggregated state, which serves at once to avoid the formation of ordered, inert amyloid fibrils, and to provide the entropic driving force for elastic recoil characteristic of rubber-like polymers (Rauscher et al., Structure 2006). Intriguingly, certain sequences have the propensity to self-assemble into either amyloid-like or elastin-like aggregates, depending on solvent conditions. In particular, certain hydrophobic elastin-like peptides can form an elastin-like film in methanol solution but amyloid in water (Flamia et al. 2004). In this study, we use atomistic molecular dynamics simulations in explicit solvent to examine solvent effects on a set of model elastin-like and amyloidogenic peptides as a means to probe the balance of structural and physical forces modulating the conformational equilibria and self-aggregation propensities of these peptides.Flamia, R., Zhdan, P.A., Martino, M., Castle, J.E., Tamburro, A.M. (2004). AFM study of the elastin-like biopolymer poly(ValGlyGlyValGly). Biomacromolecules. 5, 1511–1518.Rauscher, S., Baud, S., Miao, M., Keeley, F.W., Pomes, R. (2006). Proline and glycine control protein self-organization into elastomeric or amyloid fibrils. Structure. 14, 1667–1676.