Counter-effects of Ethanol and Cholesterol on the Heterogeneous PSM-POPC Lipid Membrane: A Molecular Dynamics Simulation Study.

In a recent work, we reported that the presence of ethanol molecules leads to significant changes on the structural stability of a homogeneous sphingomyelin bilayer. We observed that at higher concentrations of ethanol (≥20 mol %), the structure of the PSM (N-palmitoyl-sphingomyelin) bilayer is almost lost. H-bond analysis revealed that ethanol molecules form H-bonds with the PSM lipids at the cost of PSM-PSM intermolecular H-bonding interactions, subsequently leading to destabilization of the homogeneous PSM bilayer. Biological membranes are heterogeneous and anisotropic in nature. Previously, it has been reported that partitioning of amphiphilic molecules across the lipid bilayer is governed by the lipid composition and cholesterol content. In order to further enhance our understanding towards the interaction of ethanol in the heterogeneous membrane environment, herein, we have investigated the influence of 5 and 20 mol % of ethanol on the structure and stability of two heterogeneous bilayers: a binary bilayer comprising PSM and POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) lipids and a ternary bilayer consisting of cholesterol along with PSM and POPC. The study reveals that the disordering and destabilizing effects of ethanol on the binary bilayer systems are enhanced as compared to that on the homogeneous PSM bilayer. However, the presence of cholesterol mitigates the influence of ethanol on the lipid bilayer because of its condensing and ordering effects on other lipids.