Voltage sensing by dipolar transmembrane peptides.

Abstract

Transmembrane (TM) voltage plays a vital role in the behaviour and functions of the lipid bilayer membrane. It regulates the exchange of particles across the membrane through TM proteins such as voltage-gated ion channels. This work studies a novel mechanism for sensing membrane voltage, which involves the reorientation of alpha-helices present in the TM proteins with the change in the membrane voltage. We consider model dipolar peptides embedded in a lipid bilayer and perform coarse-grained molecular dynamics simulations to study the effect of variation of TM voltage on their tilt angles and ascertain the optimal parameters for designing a sensitive membrane voltage sensor. We find that the sensitivity of the VSP rises with the number of charged residues. The dependence of sensitivity on the hydrophobic length shows an optimum value of the hydrophobic length for which the sensitivity is maximum for peptides with a stronger electrical dipole. We also developed a theoretical model for the system based on phenomenological free energies to consolidate the simulations. Using the model, we explore the parameter space further and establish the dependence of voltage sensitivity on these parameters.