Molecular Simulations of Mixed Lipid Bilayers with Sphingomyelin, Glycerophospholipids, and Cholesterol.

The highly diversified composition of lipid bilayers across living cells is crucial for many biological processes. Lipid bilayers mainly consist of phosphatidylcholines (PC), phosphatidylethanolamines (PE), sphingomyelin (SM), and cholesterol, with eukaryotic membranes containing high percentage of sphingomyelin and cholesterol. In this study, we have modeled bilayers with different concentration of PC, PE, and SM to understand the changes in bilayer properties with varied SM concentrations. In addition, membrane models with 33% cholesterol have been simulated to understand the influence of cholesterol. To quantitatively access the structure and dynamics of membranes, deuterium order parameters (SCD), mass density profiles, lipid relaxation times, clustering analysis, and radial distribution functions are calculated. The SCDs compare favorably with past NMR experiments and increase with an increase in SM content. The surface area calculations showed that on addition of 50% palmitoyl-SM (PSM) surface area decreases (60.0 ± 0.6 Å2) from that of pure POPC (64.7 Å2), which is further lowered in the presence of cholesterol (44.4 ± 0.2 Å2). The lipid axial relaxation time decreases with increase in concentration of glycerophospholipids. The accuracy of these lipid membranes allows for future studies with more complex lipid mixtures containing SM to represent the diversity of lipids in natural membranes.