Bioinspired mechanosensitive ion channels: design principles and emerging applications

Mechanosensitive ion channels (MSCs) enable living systems to convert mechanical forces into electrochemical signals, thereby providing fundamental support for essential physiological processes such as touch, hearing, osmoregulation, and blood-pressure sensing. Recent advances in cryo-electron microscopy and single-molecule biophysics have revealed the structural architectures and force-gating mechanisms of diverse MSC families, including mechanosensitive channel of large conductance (MscL), Piezo, transient receptor potential (TRP), two-pore domain potassium (K2P), and osmosensitive calcium-permeable/transmembrane 63 (OSCA/TMEM63). Inspired by these natural MSCs, bioinspired MSCs (BMSCs) have emerged as a rapidly growing kind of artificial systems capable of translating membrane tension, pressure, or deformation into controllable ion transport. In this Review, we outline the structural features and mechanotransduction mechanisms of representative natural MSCs. We systematically discuss current construction strategies for BMSCs, spanning (i) electrokinetic modulation; (ii) pore/channel deformation, and (iii) molecular conformational gating. Finally, we introduce emerging applications of these systems in smart drug delivery, ultrasensitive mechanical sensing, and memristor devices. By bridging molecular mechanotransduction with synthetic nanofluidic and functional materials, BMSCs provide a versatile platform for mechanically adaptive ion transport and open new opportunities for next-generation biomaterials and intelligent electronic systems.