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.