Reciprocal Coupling among Extracellular Matrix Mechanics, Mechanosensitive Ion Channels, and Cell Remodeling...

Cells actively remodel the extracellular matrix (ECM) through a repertoire of mechanically driven behaviors, including traction force generation, migration, proteolysis, and long-term deposition. While these processes are often discussed separately, emerging evidence suggests that they are coordinated through shared mechanochemical signaling modules. In parallel, advances in hydrogel-based biomaterials have revealed that ECM mechanics, including stiffness, viscoelastic dissipation, degradability, and temporal dynamics, can systematically program cellular remodeling behaviors. In this review, we discuss the close interplay among ECM mechanics, mechanosensitive ion channels, and cell remodeling behaviors, with particular emphasis on ion channels as mechanochemical control nodes that connect material-defined mechanical cues to cytoskeletal tension, adhesion dynamics, and transcriptional reprogramming. Focusing on Piezo1, TRPV4, TRPM7, and TRPC6, we discuss how localized Ca2+ entry events decode extracellular mechanics into behavior-specific outputs across distinct remodeling modalities. We further discuss how engineered hydrogels define the mechanical environment that shapes channel-mediated signaling, thereby shaping when, where, and how ECM remodeling occurs. Together, this perspective positions mechanosensitive ion channels as a mechanochemical control layer that links dynamic material environments to coordinated cellular behaviors, highlighting their relevance to the design of biomaterials that actively direct tissue remodeling.