Effects of ion interactions with a cholesterol-rich bilayer

Abstract

Previous molecular dynamics (MD) simulations of ion-lipid interactions have focused on pure phospholipid bilayers. Many functional microdomains in membranes have a complex composition of cholesterol and phospholipids. Here, we reveal the distinctiveness of the interactions and the effects of the ions on a cholesterol-rich bilayer by performing MD simulations of a cholesterol-rich bilayer with a Na+/K+ mixture or a Na+/K+/Ca2+/Mg2+ mixture. The simulations reveal that Ca2+ maintains its dominant role in the interaction with the cholesterol-rich bilayer, but the binding affinity of Mg2+ to the cholesterol-rich bilayer is even weaker than the affinities of Na+ and K+, whereas its interaction with pure phospholipid bilayers is strong and is only slightly weaker than that of Ca2+. Additionally, it was found that the presence of additional divalent cations induces the headgroups of phospholipids to be more perpendicular to the membrane surface, reducing the lateral movement of lipids and slightly altering the ordering and packing of the cholesterol-rich bilayer, different from divalent cations, which strongly influence that ordering and packing of pure phospholipid bilayers. Therefore, this study indicates that cholesterol in the membrane could affect the interactions between membrane and cations. The findings could be helpful in understanding the biological processes relevant to regulation of cations in cholesterol-rich regions.