Molecular signatures of pressure-induced phase transitions in a lipid bilayer

TL;DR

This study uses molecular dynamics simulations to explore how lipid bilayers respond to pressure and temperature changes, revealing phase transitions, structural markers, and the accuracy of force fields in modeling membrane behavior.

Contribution

It demonstrates the effectiveness of CHARMM36 force field in accurately reproducing lipid phase boundaries and identifies key structural markers for membrane phase states.

Findings

DMPC undergoes a liquid-gel transition within studied conditions

Gauche fraction is the most robust phase marker

Interdigitated gel structure is the equilibrium under finite-size conditions

Abstract

Understanding how lipid bilayers respond to pressure is essential for interpreting the coupling between membrane proteins and their native environments. Here, we use all-atom molecular dynamics to examine the pressure-temperature behavior of model membranes composed of DMPC or $\Delta$9-cis-PC. Within the studied range (288-308 K, 1-2000 bar), DMPC undergoes a liquid--gel transition, while $\Delta$9-cis-PC remains fluid due to unsaturation. The CHARMM36 force field reproduces experimental boundaries with high fidelity: simulated DMPC transitions deviate by only 5-10 K and 100-300 bar, and $\Delta$9-cis-PC exhibits no transition. Hysteresis is modest but most pronounced when starting from low-temperature gels. We identify area per lipid, bilayer thickness, and acyl-chain gauche fraction as sensitive phase markers; among these, the gauche fraction provides the most robust signature. Simulations indicate an interdigitated gel is the equilibrium structure under finite-size conditions. However, at low temperature and high pressure, interdigitation decreases, consistent with the experimental lamellar gel phase. This long-lived interdigitation critically impacts standard order parameters, specifically area per lipid and membrane thickness. These results underscore the accuracy of modern force fields and highlight how simulations mechanistically complement experimental studies of pressure-regulated membranes.