Elastic properties and shape of the Piezo dome underlying its mechanosensory function

Abstract

In a companion paper we show that the free membrane shape of lipid bilayer vesicles containing the mechanosensitive ion channel Piezo can be predicted, with no free parameters, from membrane elasticity theory together with measurements of the protein geometry and vesicle size (accompanying paper). Here we use these results to determine the force that Piezo exerts on the free membrane and, hence, that the free membrane exerts on Piezo, for a range of vesicle sizes. From vesicle shape measurements alone, we thus obtain a force-distortion relationship for Piezo, from which we deduce Piezos intrinsic radius of curvature, 42 {+/-} 12 nm, and bending stiffness, 18 {+/-} 2.1 kB T, in free-standing lipid bilayer membranes mimicking cell membranes. Applying these estimates to a spherical cap model of Piezo embedded in a lipid bilayer, we suggest that Piezos intrinsic curvature, surrounding membrane footprint, small stiffness, and large area are the key properties of Piezo that give rise to low-threshold, high-sensitivity mechanical gating.