End Block Design Modulates the Assembly and Mechanics of Thermoresponsive, Dual-Associative Protein Hydrogels

Polymers exhibiting lower critical solution behavior in water have found broad use as thermoresponsive moieties in soft materials, particularly in biomedical applications for triggered actuation, gelation, accumulation, or release. In this work, changing the thermoresponsive block in a self-assembling hydrogel is shown to be a useful approach to control the viscoelastic behavior and mechanical reinforcement of the gel above its transition temperature. Triblock copolymers were prepared with artificial associative protein midblocks from either site-specific bioconjugation of narrowly disperse poly(N-isopropylacrylamide) (PNIPAM) or as biosynthetic genetic fusions to monodisperse elastin-like polypeptide (ELP) sequences. Both synthetic approaches yield responsively reinforceable hydrogels that can be stiffened by up to an order of magnitude to approximately 105 Pa at 30% (w/w). However, end block chemical composition and linear block copolymer architecture could be manipulated to yield high-temperature plate...