Mechanically Induced Adaptive Self‐Growing Protein Hydrogel

Abstract

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.