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

T Tingjie Xu Y Yibin Sun (Jilin University , , ,) Y Yu‐Xiang Wang (Beijing National Laboratory for Molecular Sciences Key Laboratory of Polymer Chemistry & Physics of Ministry of Education Center for Soft Matter Science and Engineering College of Chemistry and Molecular Engineering Peking University Beijing 100871 P.R. China) F Fengyi Jiang B Bo Hou (School of Chemistry and Molecular Engineering) Z Ziyi Meng (Beijing National Laboratory for Molecular Sciences Key Laboratory of Polymer Chemistry & Physics of Ministry of Education Center for Soft Matter Science and Engineering College of Chemistry and Molecular Engineering Peking University Beijing 100871 P.R. China) L Lianjie Xu (Beijing National Laboratory for Molecular Sciences, Key Laboratory of Polymer Chemistry & Physics of Ministry of Education, Center for Soft Matter Science and Engineering, College of Chemistry and Molecular Engineering, Peking University) Y Yajie Liu (Center for Retrovirus Research, The Ohio State University) W Wen‐Hao Wu (Beijing National Laboratory for Molecular Sciences Key Laboratory of Polymer Chemistry & Physics of Ministry of Education Center for Soft Matter Science and Engineering College of Chemistry and Molecular Engineering Peking University Beijing 100871 P.R. China) W Wen‐Bin Zhang (Beijing National Laboratory for Molecular Sciences Key Laboratory of Polymer Chemistry & Physics of Ministry of Education Center for Soft Matter Science and Engineering College of Chemistry and Molecular Engineering Peking University Beijing 100871 P.R. China)

Abstract

Abstract 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.

Article Details

Volume / Issue Vol. 64, Issue 48
Published November 24, 2025
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (10)

T

Tingjie Xu

Y

Yibin Sun

Jilin University , , ,

Y

Yu‐Xiang Wang

Beijing National Laboratory for Molecular Sciences Key Laboratory of Polymer Chemistry & Physics of Ministry of Education Center for Soft Matter Science and Engineering College of Chemistry and Molecular Engineering Peking University Beijing 100871 P.R. China

F

Fengyi Jiang

B

Bo Hou

School of Chemistry and Molecular Engineering

Z

Ziyi Meng

Beijing National Laboratory for Molecular Sciences Key Laboratory of Polymer Chemistry & Physics of Ministry of Education Center for Soft Matter Science and Engineering College of Chemistry and Molecular Engineering Peking University Beijing 100871 P.R. China

L

Lianjie Xu

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Polymer Chemistry & Physics of Ministry of Education, Center for Soft Matter Science and Engineering, College of Chemistry and Molecular Engineering, Peking University

Y

Yajie Liu

Center for Retrovirus Research, The Ohio State University

W

Wen‐Hao Wu

Beijing National Laboratory for Molecular Sciences Key Laboratory of Polymer Chemistry & Physics of Ministry of Education Center for Soft Matter Science and Engineering College of Chemistry and Molecular Engineering Peking University Beijing 100871 P.R. China

W

Wen‐Bin Zhang

Beijing National Laboratory for Molecular Sciences Key Laboratory of Polymer Chemistry & Physics of Ministry of Education Center for Soft Matter Science and Engineering College of Chemistry and Molecular Engineering Peking University Beijing 100871 P.R. China