Abstract

Mechanical forces are an intrinsic component of virtually all cellular functions, from cell division and migration to tissue development and organ homeostasis. Mechanosensitive (MS) ion channels serve as the fastest mechanotransducers, converting physical stimuli like membrane tension, shear stress, and osmotic shifts into electrochemical signals. This review provides a comprehensive overview of the field of mechanosensitive channels, a polyphyletic group characterized by a remarkable diversity in structural design and physiological roles. We begin by tracing the history of MS channel discovery, presenting major findings in a chronological context to illustrate the evolution of our understanding. The core of the review focuses on describing the structural features of different MS channel families, including bacterial MscL and MscS, and eukaryotic channels such as Piezo and the TRP family, highlighting the distinct mechanisms by which they sense and respond to mechanical perturbations. Finally, we synthesize the common physical principles that govern their gating mechanisms, emphasizing the critical role of the lipid bilayer and the membrane-cytoskeleton interface in channel activation. This work serves as an essential reference for researchers in membrane biophysics and cell biology, underscoring the fundamental importance of MS channels in health and disease.