Can Glucose Counterpoise the Perturbations in a Model Lipid Bilayer Containing Ethanol ?

Abstract

The biological function of cell membrane is significantly affected by a disrupted lipid bilayer. Main-taining the structural integrity of the lipid bilayer is hence crucial. In this work, a series of molecular dynamics (MD) simulations was carried out by varying ethanol and glucose concentrations to inves-tigate the counteracting effects of glucose concentration on the ethanol-stressed disorganized hy-drated model lipid bilayer, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Our work high-lights that ethanol's concentration-dependent disruptive role affects bilayer integrity, as evidenced by increased lateral diffusion, reduced bilayer thickness, and enhanced disorder in the structural ar-rangements of the lipids, including the surface curvature order parameter. We observed that the ad-dition of glucose, to some extent, opposes such disorganization. Our investigation reveals that glu-cose forms substantial hydrogen bonds with lipid headgroups, thereby reducing ethanol-headgroup interaction and, promoting tighter lipid packing. The minimum-distance distribution functions sug-gest that, while water is excluded from the lipid tail, ethanol is found all the way towards the lipid tails, and the terminal methyl groups interact significantly, causing the lipid tails to bend toward the polar regions of the bilayer. This phenomenon however was observed less in the presence of glucose. An inverse relationship between glucose concentration and translational mobility is consistently ob-served across all ethanol concentrations studied, while higher ethanol content facilitates glucose mobility, regardless of the glucose concentration. This suggests a complex interplay between glucose and ethanol that modulates the diffusive dynamics of the solvent and solute, affecting lipid diffu-sion and its structural integrity. The computation of the Potential of Mean Force (PMF) using the Umbrella Sampling technique highlights that the ethanol penetration process is significantly less fa-vored and energetically hindered in the presence of glucose; as a result, lipid diffusion is slowed down. Our findings provide insights into the molecular mechanisms and underscore the protective role of glucose in stabilizing lipid bilayers under alcohol-induced stress. The study is relevant to var-ious pharmaceutical and biomedical applications, as well as the design of biopreservation strategies for cells and tissues.