Stimuli-triggered formation of de novo-designed protein biomaterials

Protein-based biomaterials have risen in popularity in recent years owing to their genetic encodability, sequence specificity, monodispersity, and ability to interface with biological systems in comparison with synthetic polymer-based materials. Though naturally derived and minimally engineered proteins have been at the forefront of these efforts, recent advances in computational protein design offer exciting opportunities for next-generation biomaterial development. In this work, we employ de novo protein design methodologies to generate a suite of self-assembling multimeric proteins, whose step-growth heteropolymerization into bulk hydrogels and condensates can be exogenously triggered through small-molecule addition. Our results highlight how changes in programmed multimer valency and their triggered assembly yield materials with varying structures and viscoelasticity. We anticipate that these approaches will prove useful in rapidly generating large libraries of stimuli-responsive biomaterials that are precisely tailored to specific applications in the biosciences and beyond.