Phenolic compounds alter the ion permeability of phospholipid bilayers<i>via</i>specific lipid interactions
Sheikh I. Hossain, Suvash C. Saha, Evelyne Deplazes
Abstract
-coumaric acid showed no effect. Experiments with lipids lacking the phosphate group show a significant decrease in the membrane-altering effects indicating that specific phenolic-lipid interactions are critical in altering ion permeability. MD simulations confirm that compounds that alter ion permeability form stable interactions with the phosphate oxygen. In contrast, inactive phenolic compounds are superficially bound to the membrane surface and primarily interact with interfacial water. Our combined results show that compounds with similar structures can have very different effects on ion permeability in membranes. These effects are governed by specific interactions at the water-lipid interface and show no correlation with lipophilicity. Furthermore, none of the compounds alter the overall structure of the phospholipid bilayer as determined by area per lipid and order parameters. Based on data from this study and previous findings, we propose that phenolic compounds can alter membrane ion permeability by causing local changes in lipid packing that subsequently reduce the energy barrier for ion-induced pores.