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

Abstract

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 (S), mass density profiles, lipid relaxation times, clustering analysis, and radial distribution functions are calculated. The Ss 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 Å) from that of pure POPC (64.7 Å), which is further lowered in the presence of cholesterol (44.4 ± 0.2 Å). 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.

Clustering and dynamics of crowded proteins near membranes and their influence on membrane bending

“…Lipid order parameters as a function of protein concentration (SI Appendix, Fig. S33) were found to be very similar values to previous results for pure POPC-sphingomyelincholesterol mixtures with the same force field that was used here (48). Protein concentration had virtually no effect, indicating that the internal structure and dynamics of the lipid bilayer and the liquid-ordered state expected for the lipid composition in this study are not affected by the presence of the proteins.…”

Comparison of Additive and Polarizable Models with Explicit Treatment of Long-Range Lennard-Jones Interactions Using Alkane Simulations

“…The FF has also been tested with lipid mixtures containing cholesterol with glycerophospholipids and/or sphingolipids, and agrees with X-ray form factors and NMR order parameters. 10–13 This has allowed for accurate interpretations of liquid ordered/disordered phases of lipid mixtures 14 and lipid composition effects on hydrogen bonding and lipid clustering. 12, 13 Although simulations with the C36 lipid FF have been successful, the FF does have inherent flaws.…”

Microscopic view of lipids and their diverse biological functions

“…Several extensive MD studies have shown that their presence affects the packing and thickness of the membrane, as well as its phase-transition temperature [6–9]. At certain concentrations, CHL and SM increase lipid ordering and decrease surface area, consequently increasing membrane condensation [10]. These effects were also found by MD studies to modulate transport properties, e.g., the permeability of small molecules, even nonpolar gases, through a lipid bilayer [11] and membrane dipole potentials [12].…”