Regulation of ion channels by membrane domains

Cells must respond to external signals. The perception of mechanical stimuli is often linked to the activation of ion channels in the plasma membrane. Some of these channels can open in response to traction, i.e., an increase in membrane tension, and thus trigger a corresponding cellular response or stimulus transmission. Since these channels are embedded in lipids, the mechanical properties of the lipids are likely to play a significant role. In the present project, we want to investigate how the preferential residence of the channels in membrane areas with ordered or disordered lipids affects the opening probability. We will also investigate to what extent membrane asymmetry, i.e., the different components of the two membrane monolayers, affects channel gating. In addition, we plan to explore the influence of membrane elasticity on the sensitivity threshold of potassium and sodium channels. For this purpose, we will purify the channels and reconstitute them in lipid bilayers. We will flank the electrophysiological measurements with fluorescence microscopy images to detect the channel location. We will measure the elastic properties of the membranes by partially aspirating cell-sized lipid vesicles into micropipettes with varying degrees of suppression. From these studies, we hope better to understand the interaction of lipids with membrane proteins. The latter is essential for determining molecular causes of pathological conditions and the development of therapeutic approaches.