Mechanically Induced Adaptive Self-Growing Protein Hydrogel.

Abstract

Living tissues strengthen under repeated mechanical loading, yet replicating such adaptive growth in synthetic materials remains a formidable challenge. Here, we report a protein-based hydrogel that undergoes mechanochemically induced self-growth, autonomously reinforcing its baseline mechanical properties under applied stress. This strategy harnesses the copper-storage protein Csp1, whose force-regulated unfolding releases Cu(I) that catalyzes in situ azide-alkyne cycloaddition, generating secondary crosslinks under mechanical load. Upon unloading, Csp1 refolds and re-sequesters Cu(I), halting catalysis and restoring growth capacity. This mechano-catalytic feedback loop enables stress- and time-dependent self-reinforcement within a closed system, without external monomer supply. The hydrogel exhibits programmable mechanical memory via leveraging Cu(I) homeostasis in cyclic growth-pause-growth transitions. By coupling force-dependent protein conformational dynamics with catalytic activity, this strategy establishes a generalizable mechanochemical framework for designing self-adapting biomaterials whose structure and function evolve under mechanical stimulation.