Study of lipid heterogeneity on bilayer membranes using molecular dynamics simulations.

Human cell membranes consist of various lipids that are essential for their structure and function. It typically comprises phosphatidylcholine (POPC), phosphatidylethanolamine (POPE), phosphatidylserine (POPS), sphingomyelin (PSM), and cholesterol (CHL). Several experimental and computational techniques have been employed to characterize the composition of human cell membranes, however, CHL enriched membrane is still not clearly understood through these techniques. Molecular dynamics simulation results illustrated the biophysical properties of heterogeneous membranes based on the lipid composition as well as the concentration of lipids, exclusively for CHL and PSM. Herein, we have investigated the structure-function relationships of lipids comparatively to delineate the effect of heterogeneity on the biophysical properties of different membranes. It has been observed that the significant fraction of CHL (i.e., ~33% in ternary, ~25% in quaternary, and ~16% in senary type bilayers) in combination with other lipids introduced compactness, and increased the thickness of the membrane. The analysis of lipid mass density stated that the density of lipid head group, phosphate , and glycerol-ester in presence of CHL with or without PSM is an underlying reason for membrane ordering. Results also revealed that the presence of POPI and POPS are the reasons for an adequate drop in the ordering of lipid chain, particularly on POPE chain. The self-interaction of CHL, PSM, POPE and the interaction of CHL and POPC with POPE seem to determine the structure and function of the heterogeneous membrane. Our findings provide a qualitative understanding of the effect of membrane heterogeneity on the physiological properties of membranes. The structures inspected in this study would help to select the heterogeneous bilayer model to mimic the human cell membranes to analyse or characterize the membrane-associated phenomena. [Display omitted] • Structure-function relationship of lipids to delineate the effect of heterogeneity on the biophysical properties of membranes. • The membrane ordering depends on the density of lipid head group, phosphate, and glycerol-ester in presence of CHL with or without PSM. • Results also revealed the POPI and POPS are the reasons for an adequate drop in the ordering of lipid chain particularly of POPE chain. [ABSTRACT FROM AUTHOR]