Mechanics of force sensing in Piezo ion channels

Since their discovery in 2010, it has been discovered that Piezo proteins provide the molecular basis for many different forms of mechanosensation, including the sensation of touch in humans. Piezo ion channels are mechanosensitive ion channels that locally bend the membrane into a spherical cap that can, in turn, produce a large membrane footprint. Previous work has shown that the shape of Piezo's membrane footprint can be predicted quantitatively through membrane elasticity theory, that the Piezo protein is similarly flexible as a typical lipid bilayer membrane, and that Piezo's gating properties emerge from the interplay of Piezo structure, membrane shape, and the mechanics of the Piezo-membrane system. Building on this previous work, we develop a simple analytic model of Piezo gating, which we test against fully nonlinear, numerical solutions. This model provides us with straightforward mathematical expressions describing the dominant physics of Piezo's response to lateral membrane tension. We then extend the theory to account for vertical forces exerted onto the membrane by, for instance, the cytoskeleton. We employ this generalized theory to systematically explore the modulation of Piezo's gating response by vertical forces on the cell membrane.