Electrostatic Determinants of Membrane Ion Permeability

Abstract

Ion channels facilitate the passage of charged molecules across cell membranes by eliminating energetic costs thought to be associated with dehydration inside a low-dielectric membrane core. However, recent atomistic simulation studies have uncovered a different picture of charge-lipid interactions with reduced barriers due to membrane deformations. Having a correct description of the origins and magnitudes of these energetic barriers is essential to describe ion permeation, as well as to understand processes that involve the interaction of charged peptides or protein domains with membranes. Here we seek energetic decompositions to unveil the mechanisms of assisted or unassisted permeation and explore the roles of membrane electronic polarizability, dipole potential and composition (including charged lipids). We find that while electronic polarizability has some considerable effects on ion solvation free energies in non-polar solvents, as well as solvent interfacial potentials, a polarizable lipid model reveals only small effects on ions in the membrane. We show that the full membrane dipole potential is not seen by ions and explore the role of the membrane electrostatics on ions inside ion channel proteins.