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 dimyristoylphosphatidylcholine (DMPC) or its cis-unsaturated analogue
Δ9-cis-PC. Within the studied range (288–308 K, 1–2000
bar), DMPC undergoes a liquid–gel transition, while Δ9-cis-PC
remains fluid due to unsaturation. The CHARMM36 force field reproduces
experimental boundaries with high fidelity: simulated DMPC transitions
fall within 5–10 K and 100–300 bar of experimental values,
and Δ9-cis-PC exhibits no transition. Hysteresis is modest but
most pronounced when starting from low-temperature gels; we propose
a split-phase simulation protocol that alleviates the hysteresis problem.
We identify the area per lipid, bilayer thickness, and acyl-chain
gauche fractions as sensitive phase markers; among these, the gauche
fraction provides the most robust signature. Simulations indicate
that an interdigitated gel is the equilibrium structure under finite-size
conditions, and we propose a novel metric to quantify the extent of
this phenomenon. 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. Finally, we discuss
in detail how finite-size effects influence phase transition and interdigitation.
Overall, these results underscore the accuracy of modern force fields
and highlight how simulations are essential to mechanistically complement
experimental studies of pressure-sensitive membranes.