The interplay between ordered and disordered domains is critical in biological materials. To investigate the impact of the interplay of order and disorder at the sequence level on macroscopic material properties, we designed a set of partially ordered polypeptides (POPs) in which we precisely tune the order and disorder in their secondary structure at their primary —amino acid— sequence level. The stimuli-responsiveness of the disordered components consisting of an elastin-like polypeptide (ELPs), and the structural stability of their ordered domains consisting of polyalanine helices, combine to produce materials with emergent properties not exhibited by materials that consist of each sequence alone. POPs are thermally-responsive polypeptides that exhibit lower critical solution temperature (LCST) phase behavior in aqueous solvents, but exhibit, unlike ELPs, thermal hysteresis in their transition temperature. Upon undergoing their LCST transition, POPs form an interconnected, porous, fractal-like network that is physically crosslinked and behaves as a viscoelastic solid. We have further explored the mechanisms driving these interactions using molecular dynamics simulations. Upon sub-cutaneous injection of liquid POPs that are designed to have a transition temperature below body temperature, the POPs form a stable scaffold that rapidly integrates into surrounding tissue with minimal inflammation or fibrous capsule formation and a high degree of vascularization. This work demonstrates that the modulation of order and disorder at the sequence level is a new and useful principle for the design of functional protein biomaterials.

Modulation of order and disorder in the sequence of a genetically encoded polypeptide yields injectable porous network

254th National Meeting (2017)

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