Concentration-Driven Alterations in Lipid Bilayer Behavior by Interfacial Glucose: An MD Perspective

Abstract

Lipid bilayers are essential components of biological membranes, maintaining structural integrity and facilitating processes like signaling, transport, and membrane remodeling. Certain organisms can withstand anhydrobiotic conditions due to high intracellular concentrations of saccharides, which help protect membranes.1-2 While some saccharides are known to stabilize membranes, the molecular-level mechanisms remain unclear and appear to be concentration dependent. In this study, atomistic molecular dynamics (MD) simulations were used to explore the effect of glucose concentration (0–30 wt%) on a hydrated DMPC lipid bilayer in 0.3 M NaCl solution. Glucose molecules intercalate between lipid headgroups, decreasing bilayer thickness while increasing the lateral area per lipid, indicating a crowding effect. This crowding enhances membrane undulations, compresses lipid tails, and raises the area compressibility modulus, implying increased membrane rigidity. At higher glucose concentrations, significant bilayer curvature emerges, captured through a grid-based surface evaluation method.3-4 Hydrogen bonding dynamics show a concentration-dependent restructuring: lipid–glucose bonds become shorter-lived, while lipid–water bonds become more stable with increasing glucose. These molecular interactions also reduce lipid lateral diffusion and alter tail ordering, underscoring how glucose modifies bilayer physical properties. Our findings showed that glucose at the membrane interface modulates bilayer behavior through a multifaceted interplay of crowding, hydrogen bonding, and curvature generation. These insights provide a mechanistic understanding of saccharide-mediated membrane stabilization, with potential implications for cryoprotection strategies, drug delivery systems, and the design of biomimetic membranes.