Behavior of water at lipid/water interfaces upon phase transition of the lipid bilayer: Insights from 1D- and 2D-vibrational sum frequency generation spectral calculations from molecular dynamics simulations.

This article focuses on the structural and dynamical behavior of interfacial water molecules near 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) lipid bilayers across temperatures spanning the gel to liquid phase transition (285–320 K). Using molecular dynamics simulations combined with one-dimensional (1D) and two-dimensional (2D) vibrational sum frequency generation (VSFG) spectral calculations, the study reveals that water molecules orient predominantly upward toward the bilayer, influenced mainly by the negatively charged phosphate groups despite DMPC's zwitterionic nature. The absence of dangling O–H peaks in the spectra indicates strong hydrogen bonding between water and lipid headgroups. Dynamical analyses via 2D-VSFG and frequency fluctuation time correlation functions show a distinct dynamical crossover at the lipid melting temperature, with differing activation energies for spectral diffusion before (∼6.6 kcal/mol) and after (∼4.3 kcal/mol) the phase transition, reflecting changes in the interfacial water environment. These findings highlight the utility of 2D-VSFG spectroscopy in probing water dynamics associated with phase transitions at biologically relevant membrane interfaces.