MECHANISM OF UNASSISTED ION-TRANSPORT ACROSS MEMBRANE BILAYERS

To establish how charged species move from water to the nonpolar membr ane interior and to determine the energetic and structural effects acc ompanying this process, we performed molecular dynamics simulations of the transport of Na+ and Cl- across a lipid bilayer located between t wo water lamellae. The total length of molecular dynamics trajectories generated for each ion was 10 ns. Our simulations demonstrate that pe rmeation of ions into the membrane Is accompanied by the formation of deep, asymmetric thinning defects in the bilayer, whereby polar lipid head groups and water penetrate the nonpolar membrane interior. Once t he ion crosses the midplane of the bilayer the deformation ''switches sides''; the initial defect slowly relaxes, and a defect forms in the outgoing side of the bilayer. Af a result, the ion remains well solvat ed during the process; the total number of oxygen atoms from water and lipid head groups in the first solvation shell remains constant. A si milar membrane deformation is formed when the ion is instantaneously i nserted into the interior of the bilayer. The formation of defects con siderably lowers the free energy barrier ru transfer of the ion across the bilayer and, consequently, increases the permeabilities of the me mbrane to ions, compared to the rigid, planar structure, by approximat ely 14 orders of magnitude. Our results have implications for drug del ivery using liposomes and peptide insertion into membranes.