Role of Ion-Phospholipid Interactions in Zwitterionic Phospholipid Bilayer Ion Permeation.

Despite the central role of Na+ and K+ in physiological processes, it is still unclear whether they interact or alter the physical properties of simple zwitterionic phospholipid bilayers at physiologically relevant concentrations. Here we report a difference in membrane permeability between Na+ and K+, as measured with electrical impedance spectroscopy and tethered bilayer lipid membranes. We reveal that the differences in membrane permeability originate from distinct ion coordination by carbonyl oxygens at the phospholipid-water interface, altering the propensity for bilayer pore formation. Molecular dynamics simulations showed differences in the coordination of Na+ and K+ at the phospholipid-water interface of zwitterionic phospholipid bilayers. The ability of Na+ to conscript more phospholipids with a greater number of coordinating interactions causes a higher localized energy barrier for pore formation. These results provide evidence that ion-specific interactions at the phospholipid-water interface can modulate the physical properties of zwitterionic phospholipid bilayers.