Ion-Induced Defect Permeation of Lipid Membranes

by Vorobyov, I.; Olson, T. E.; Kim, J. H.; Koeppe, R. E.; Andersen, O. S.; Allen, T. W.

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 freeenergy 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 membraneactive peptides and proteins.

Journal
Biophysical Journal
Volume
106
Issue
3
Year
2014
Start Page
586-597
URL
https://dx.doi.org/10.1016/j.bpj.2013.12.027
ISBN/ISSN
1542-0086; 0006-3495
DOI
10.1016/j.bpj.2013.12.027