Molecular dynamics simulations of membrane-sugar interactions

Area of Science:

• Biophysics
• Computational Chemistry
• Materials Science

Background:

• Disaccharides, especially trehalose (TRH), are known to influence lipid bilayer physical properties and functionality.
• Understanding these interactions is crucial for applications in drug delivery, cryoprotection, and biomaterial design.

Purpose of the Study:

• To investigate the molecular interactions between trehalose (TRH) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid bilayers.
• To quantify the effect of TRH concentration on bilayer structure, dynamics, and mechanical properties.
• To compare simulation results with experimental data and analytical models.

Main Methods:

• Molecular dynamics (MD) simulations were employed to model DMPC bilayers with varying trehalose concentrations (wTRH = 0-0.20).
• Potential of Mean Force (PMF) calculations were performed using two distinct force fields to determine interaction energies.
• An analytical model was developed to describe sugar binding at the membrane interface, validated against MD results.

Main Results:

• Increased trehalose concentration led to increased area per lipid and membrane thinning, indicating TRH intercalation into the lipid polar headgroups.
• The compressibility modulus significantly increased with TRH concentration, suggesting enhanced bilayer order and rigidity.
• Lateral diffusion of lipids decreased by a factor of 15, consistent with the formation of a glassy state at the membrane interface.

Conclusions:

• Molecular dynamics simulations and an analytical model accurately describe trehalose-lipid bilayer interactions.
• Trehalose induces significant structural and dynamic changes in DMPC bilayers, leading to increased rigidity and a potential glassy state.
• The findings align with experimental observations and provide molecular insights into membrane-sugar interactions.