title: Ion-induced defect permeation of lipid membranes.
abstract: We have explored the mechanisms of uncatalyzed membrane ion permeation using atomistic simulations and electrophysiological recordings. The solubility-diffusion mechanism of membrane charge transport has prevailed since the 1960s, despite inconsistencies in experimental observations and its lack of consideration for the flexible response of lipid bilayers. We show that direct lipid bilayer translocation of alkali metal cations, Cl(-), and a charged arginine side chain analog occurs via an ion-induced defect mechanism. Contrary to some previous suggestions, the arginine analog experiences a large free-energy barrier, very similar to those for Na(+), K(+), and Cl(-). Our simulations reveal that membrane perturbations, due to the movement of an ion, are central for explaining the permeation process, leading to both free-energy and diffusion-coefficient profiles that show little dependence on ion chemistry and charge, despite wide-ranging hydration energies and the membrane's dipole potential. The results yield membrane permeabilities that are in semiquantitative agreement with experiments in terms of both magnitude and selectivity. We conclude that ion-induced defect-mediated permeation may compete with transient pores as the dominant mechanism of uncatalyzed ion permeation, providing new understanding for the actions of a range of membrane-active peptides and proteins.
authors: Department of Chemistry, University of California, Davis, Davis, California.
authors: Igor
authors: I
authors: Vorobyov
authors: Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York.
authors: Timothy E
authors: TE
authors: Olson
authors: Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York.
authors: Jung H
authors: JH
authors: Kim
authors: Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas.
authors: Roger E
authors: RE
authors: Koeppe
authors: Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York. Electronic address: sparre@med.cornell.edu.
authors: Olaf S
authors: OS
authors: Andersen
authors: School of Applied Sciences and Health Innovations Research Institute, RMIT University, Melbourne, Victoria, Australia; Department of Chemistry, University of California, Davis, Davis, California. Electronic address: toby.allen@rmit.edu.au.
authors: Toby W
authors: TW
authors: Allen
mesh_terms: D002712:Chlorides / Q000378:metabolism*; D017136:Ion Transport; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D010539:Permeability; D011188:Potassium / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
chemical_list: D002712:Chlorides; D008051:Lipid Bilayers; D012964:Sodium; D011188:Potassium