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.