Synergic Effects of Glucose and Trehalose on Hydrated Lipid Bilayer Properties

Abstract

The lipid bilayer is a crucial component of biological cell membranes, and proper hydration is essential for maintaining its normal functions within cells. It is hypothesized that saccharides such as glucose, sucrose, and trehalose offer protection to membranes, preventing cell rupture and stabilizing lipid membranes in aqueous environments.1-3 However, this protective effect is influenced by the concentration of saccharides, and the detailed molecular interactions between saccharides and lipids are still not fully understood. In this study, we conducted a series of molecular dynamics (MD) simulations to investigate the effects of varying concentrations of glucose4 and trehalose on the structure and dynamics of hydrated 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers. We explored a range of glucose and trehalose concentrations, both individually and in combination, in the presence of physiological concentrations of NaCl. Biological membranes are highly dynamic and rarely planar, that plays a crucial role in essential cellular processes, including endocytosis, membrane fusion and fission, trafficking, and remodelling. We incorporated curvature effects in our analysis using a grid-based approach5 to quantify deviations in key structural features of the bilayer at different saccharide concentrations. Our findings indicate that the stability of the curved bilayer surface is influenced by lipid lateral diffusion, which is affected by the saccharide combinations. We observed that the area compressibility modulus increases with higher concentrations of glucose and trehalose, leading to enhanced bilayer rigidity. The preferred orientation of interactions of the saccharides with the lipid headgroups were identified, revealing that these interactions promote the formation of direct hydrogen bonds between the saccharides and the lipid headgroups.