Effect of Acyl Chain Variation and Cholesterol on Structural and Dynamic Properties of Lipid Bilayer Probed by Simulation

Lipid ordering plays a crucial role in maintaining the mechanical strength of the lipid bilayer, which is influential in controlling biological functions. This is associated with the well-known phenomena of “phase state behavior” of the bilayer. The significant factors that influence phase state behavior are stimuli such as cholesterol, physiological conditions like temperature and pH, and the structure of the lipid molecule itself, which can differ either in the head group or the acyl chain. The cholesterol concentration influences the phase state behavior and the ordering of the lipid bilayer. In this paper, we investigate the behavior of Phosphatidylcholine lipids with cholesterol, using Coarse-Grained Molecular Dynamics Simulation. The simulation is performed using a CGMartini force field. The production run of all successful simulations is completed with the same biological condition with a total runtime of 12 µs. We chose four lipids namely DLPC, POPC, DGPC, and DIPC with varied acyl chain chemical structures and investigated the influence of cholesterol. We have calculated bilayer thickness, area per lipid, order parameter, radial distribution function, and partial density which are a measure of bilayer phase state behavior. The results indicate efficient cholesterol packing in DLPC, while POPC exhibits variations due to its asymmetric acyl chain structure, which contains a single double bond in one of the chains. In contrast, DGPC and DIPC display lower order parameters, attributed to the presence of multiple double bonds in their acyl chains, which disrupt ordered packing. This study elucidates the importance of the acyl chain structure and the cholesterol composition on the phase state behavior of the lipid membrane.