Membrane Forces Regulate Voltage Sensor Movement

Abstract

Positively charged proteins, called voltage sensors, regulate the gating of voltage-sensitive ion channels. These channels have been traditionally believed to be sensitive to the local electrochemical environment. A growing number of experiments now conclusively show that lipid-associated stimuli can control the channel response. To gain insight into the mechanosensitive response exhibited by these channels, we model the interactions of a charged protein with the surrounding lipids. Our model reveals a new mechanism by which lipid-dependent electromechanical forces regulate the movement of a charged protein within a bilayer. This mechanism can potentially help in understanding and consolidating several experimental findings which demonstrate lipid-dependent shifts in voltage-sensititive ion channel gating.