Global and Specific Interactions between Mechanosensitive Ion Channels and the Lipid Bilayer

Abstract

Mechanosensitive (MS) ion channels are the primary molecular transducers of mechanical force into biologically meaningful intracellular signals [1, 2]. These force-gated channels have been implicated in numerous mechanotransduction processes ranging from cellular osmoregulation to touch and hearing. Much of our understanding of the principles that govern the conversion of mechanical force into conformational changes in MS channels comes from studies of MS channels reconstituted into liposomes [3]. These liposome reconstitution methods have enabled detailed investigation of structure-function relationships in MS channels as well as enabling researchers to probe specific protein-lipid interactions [4]. Here, we focus on the use of these methods in combination with both electrophysiological and fluorescence spectroscopy based techniques to study the structural dynamics of the bacterial MS channels MscL and MscS. In a top down approach, we show examples of how both global and specific interactions between these channels and the lipid bilayer play a crucial role in modulating their function [5, 6, 7]. This knowledge of the basic biophysical principles of mechanosensitivity acquired through the studies of MscL and MscS is also eminently applicable to eukaryotic MS ion channels including Piezo1 [8].