Lipid transmembrane asymmetry and intrinsic membrane potential: Two sides of the same coin

To better understand the origin of intrinsic membrane potential in cells, we have performed atomic-scale molecular dynamics simulations of an asymmetric lipid membrane comprised of zwitterionic (neutral) phosphatidylcholine (PC) and phosphatidylethanolamine (PE) leaflets in the absence of salt. It turns out that the asymmetry in distribution of zwitterionic lipids across the membrane gives rise to a nonzero intrinsic potential difference of about 100 mV between the two sides of the membrane. This potential arises from the difference in dipole moments of the two leaflets of the asymmetric PC/PE membrane. Our findings suggest that the transmembrane lipid asymmetry typical of most living cells can contribute to the membrane potential.