A High Modulus, Multi‐Stimuli Responsive, Interwoven Protein Network With Topologically Confined Micro‐Association

All-protein-based materials are attractive for their genetic encodability, precise structure, and versatile functions, yet integrating mechanical strength, dynamic adaptability, and functional activity in one system remains challenging. Herein, we report a multi-stimuli-responsive, self-healing, all-protein-based network with an interwoven network topology, whose mechanics can be further reinforced by topologically confined micro-association upon tempering. The network was constructed by polymerizing pseudo[2]catenanes-which employ p53dim for entanglement and SpyTag(DA)-SpyCatcher complex for physical cyclization-that are opened into a star-like conformation. Network formation can be triggered by increasing concentration, calmodulin (CaM) binding, or light irradiation (when azoswitch-modified CaM is used). Subsequent tempering unfolds the SpyTag/SpyCatcher complex, inducing micro-association that acts as additional crosslinks within the topologically confined network. While the entangled architecture minimizes chain slippage, the micro-associations enhance crosslinking and stress dissipation, collectively improving mechanical properties and long-term stability. We further demonstrate its practical utility in controlled release and enzyme immobilization, establishing topological proteins as a versatile platform for designing genetically programmable, mechanically tunable, stimuli-responsive biomaterials.