Phase Behavior and Self-Assembly of a New Family of Stimulus Responsive Peptide Polymers

Abstract

Elastin like polypeptides (ELPs), composed of repeats of VPGXG pentapeptides that recur in all tropoelastin sequences, are the best studied class of peptide polymers that exhibit lower critical solution temperature (LCST) phase behavior in water, and these polymers have enabled innovative approaches to nanoparticle self-assembly, cancer therapy, regenerative medicine and protein purification These prototypical ELPs, show aqueous coacervation behavior above their cloud point, leading to the formation of a polymer rich phase and a second, largely aqueous phase. To investigate the origins of coacervation in these systems, we asked the question, how is LCST phase behavior encoded in peptide polymers at their amino acid —primary— sequence level? To understand the sequence determinants of LCST phase behavior, we used bioinformatics to guide the synthesis of a large family of peptide polymers that are predicted to exhibit LCST phase behavior. Analysis of the LCST phase behavior of these polymers provides sequence heuristics to encode LCST phase behavior in intrinsically disordered peptide polymers and enables the design of polymers that encode two orthogonal functions —phase behavior and bioactivity— seamlessly at the primary sequence level. These studies also identified polymers that display tunable degrees of thermal hysteresis in their LCST phase behavior, a property that is exploited for the design of thermal “shape memory” nanoparticles.