Can glucose counterpoise the perturbations in a model lipid bilayer containing ethanol?

Abstract

The biological function of the cell membrane is significantly affected by a disrupted lipid bilayer. Maintaining the structural integrity of the lipid bilayer is hence crucial. In this work, a series of molecular dynamics (MD) simulations were carried out by varying ethanol and glucose concentrations to investigate the counteracting effects of glucose concentration on the ethanol-stressed disorganized hydrated model lipid bilayer, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Our work highlights that the ethanol's concentration-dependent disruptive role affects bilayer integrity, as evidenced by increased lateral diffusion, reduced bilayer thickness, and enhanced disorder in the structural arrangements of the lipids, including the surface curvature order parameter. We observed that the addition of glucose, to some extent, opposes such disorganization. Our investigation reveals that glucose forms substantial hydrogen bonds with lipid headgroups, thereby reducing ethanol–headgroup interaction and promoting tighter lipid packing. The minimum-distance distribution functions suggest 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 observed 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 diffusion 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 favored 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 various pharmaceutical and biomedical applications, as well as the design of biopreservation strategies for cells and tissues.