Paper detail

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

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 $Δ$9-cis-PC. Within the studied range (288-308 K, 1-2000 bar), DMPC undergoes a liquid--gel transition, while $Δ$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 $Δ$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.