Mechanosensitive Channel Activation by Diffusio-Osmotic Force

Abstract: For ion channel gating, the appearance of two distinct conformational states and the discrete transitions between them is essential, and therefore of crucial importance to all living organisms. We show that the physical interplay between two structural elements that are commonly present in bacterial mechanosensitive channels, namely a charged vestibule and a hydrophobic constriction, creates two distinct conformational states, open and closed, as well as the gating between them. We solve the nonequilibrium Stokes-Poisson-Nernst-Planck equations, extended to include a molecular potential of mean force, and show that a first order transition between the closed and open states arises naturally from the diffusio-osmotic stress caused by the ions and water inside the channel and the elastic restoring force from the membrane. Our proposed gating mechanism is likely to be important for a broad range of ion channels, as well as for biomimetic channels and ion channel-targeting therapeutics.