Polyrotaxanes Send Shuttling Signals.

Mimicking intercellular communication by dynamically presenting signaling molecules to cells is central to understanding biological processes and building artificial life systems. However, precise replication and control of such communication at the molecular level in synthetic environments remain largely unexplored. Here, we present a polyrotaxane-based, molecular machine-like platform that regulates shuttling motions of signaling ligands within a mechanically interlocked network. This molecularly dynamic presentation of topological constrained signals directs T cell differentiation and significantly enhances therapeutic efficacy in vivo. Mechanistic studies reveal how T cells sense and transduce dynamic molecular motions into distinct intracellular responses, demonstrating that identical ligands can produce divergent outcomes depending on their molecular dynamics. These findings establish molecular motion as a critical determinant of intercellular signaling and provide a framework for engineering artificial dynamic systems that precisely control cell fate, opening new avenues for therapeutic applications based on molecular machine principles.