Molecular packing in 1-hexanol-DMPC bilayers studied by molecular dynamics simulation

Area of Science:

• Biophysics
• Computational Chemistry
• Membrane Biophysics

Background:

• Understanding solute interactions within lipid bilayers is crucial for membrane function.
• Dimyristoyl phosphatidylcholine (DMPC) is a common model lipid bilayer system.
• 1-hexanol acts as a model
• mismatched
• solute to probe membrane properties.

Purpose of the Study:

• To investigate the structural and molecular packing effects of 1-hexanol within DMPC lipid membranes.
• To elucidate the changes in local density and molecular packing upon solute partitioning.
• To compare simulation results with experimental data for validation.

Main Methods:

• Molecular dynamics (MD) simulations of DMPC-hexanol mixtures and pure systems.
• Analysis of Voronoi volumes to quantify local density and molecular packing.
• Calculation of partial molar volumes and volume changes.

Main Results:

• 1-hexanol molecules favorably partition into the DMPC bilayer, with average location and orientation matching experimental findings.
• A positive volume change (ΔV(m) ≈ 4 cm³ mol⁻¹) was observed upon hexanol partitioning, aligning with experimental values.
• Hexanol increases its own packing density but significantly loosens lipid packing, especially in the bilayer core, leading to an overall volume expansion.

Conclusions:

• The partitioning of 1-hexanol into DMPC membranes results in a net increase in bilayer volume due to significant lipid loosening.
• Distinct depth-dependent changes in molecular packing occur: the outer interfacial region shows stretching, while the bilayer core thins and expands laterally.
• The study provides atomic-level insights into solute-lipid interactions and their impact on membrane structure and dynamics.