Origins of Non-Selective Ion Transport across Lipid Bilayers

Abstract

The theoretical description of charge transport across biological membranes has remained largely unchanged since the 1960's. However, it is widely accepted that the barriers for unassisted ion permeation via a solubility-diffusion mechanism are too high, and too selective to explain experimental observations, leading to a favoring of a non-selective transient pore process. We demonstrate that an ion-induced defect mechanism, intermediate between these two processes, can yield reduced free energy barriers with little influence of hydration free energy or the membrane dipole potential. We report experimental and computational data for a range of alkali metal, halide and charged amino acid analog molecules. Our simulations reveal that membrane perturbations are central in explaining the shape and magnitude of the free energy barriers, the similarity for ions of different size, charge and chemistry, and for obtaining fluxes consistent with experiment. We will discuss results that suggest a transition from ion-induced defect to the solubility-diffusion mechanism in thicker bilayers, and for larger hydrophobic ions and ionophores. We explore the deformable membrane description to predict a greater common energetics for a range of ions, poly-ions and zwitterions and discuss the consequences for membrane interactions with charged peptides and proteins, and the roles of lipid components in membrane ion transport.