Lipid molecules that can assemble into bilayers and provide the basic structure for all cellular membranes. The diversified composition of lipids in cellular membranes is crucial for many biological processes. Lipid membranes mainly consist of phosphatidylcholines (PC), phosphatidylethanolamines (PE), sphingomyelin (SM) and cholesterol, with eukaryotic membranes containing high percentage of SM 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 concentration. Also, bilayer models with 33% cholesterol have been studied to understand the influence of higher cholesterol content on membrane biophysics. To quantitatively access the structure and dynamics of membranes, deuterium order parameters (SCD), density profiles, lipid relaxation times, clustering analysis, and radial distribution functions are calculated after a minimum 300ns molecular dynamics (MD) runs. The CHARMM36 all-atom FF, well suited for studying dynamic behavior of lipid bilayers were used for molecular simulations. The SCDs compare favorably with past NMR experiments and show an increase in SCD with an increase in SM and further in presence of cholesterol. 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 presence of cholesterol (44.4±0.2 Å2). Sphingomyelin and cholesterol results in development of more ordered lipid phases which was validated with overall decrease in SA/lipid and increase in order parameters in these model systems studied. Lipid clustering which estimates the local packing of head groups in the bilayer, shows a web-like arrangement of lipids in the bilayer containing POPE, suggesting an interaction network formed due to the intermolecular hydrogen bonds of POPE with PSM and cholesterol. Whereas in the system with POPC, a clumped arrangement of lipids lacking the web-like connection of lipids is found, as POPC forms less hydrogen bonds with PSM. It was found that higher concentration of PSM slows the axial motion of the lipids which is further slowed down in presence of cholesterol. The accuracy of these lipid membranes demonstrates that future studies with more complex lipid mixtures containing sphingomyelin to represent the diversity of lipids in natural membranes can be performed.

All-atom simulation studies on lipid bilayers, composed of sphingomyelin, glycerophospholipids and cholesterol

254th National Meeting (2017)

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