In this collaboration between high-resolution inelastic X-ray scattering (IXS) and all-atom molecular dynamics (MD) simulation, we computed the phonon dispersions from both IXS spectroscopy and MD simulation for ternary mixtures of dioleoyl phosphocholine (DOPC)/dipalmitoyl phosphatidylcholine (DPPC)/cholesterol (Chol) (an unsaturated lipid, a saturated lipid, and cholesterol) in both the liquid-ordered and liquid-disordered phases. Our analysis revealed an optic-like phonon mode present in the liquid-ordered (Lo) phase but not present in the liquid-disordered phase. This mode was gapped at low Q, around 5 nm⁻¹. The optical nature of this mode means that it must be a collective excitation that involves more than one type of molecule. The Q range of the gap indicates that there are ordered regions in the Lo phase that contain several lipids.

 The cover image of the December 3 issue of Biophysical Journal shows these regions as black circles. The colored symbols are the in-plane projected centers of mass of the hydrocarbon chains and cholesterol (the blue squares are DOPC, the red circles are DPPC, and the yellow triangles are Chol). Positions were obtained from one leaflet in the Lo phase, from one frame of the MD simulation. The gray and black circles have a diameter of 1.3 nm, corresponding to the gap distance for the Lo optical mode, as found in both simulation and experiment. Thus, these regions are examples of the largest regions that do not support this optical mode. This IXS-MD integrated analysis is possible only because of the recent convergence of IXS sensitivity and computational capabilities for MD simulation.

 — James E. Fitzgerald III, Dmytro Soloviov, Yong Q. Cai, Frederick A. Heberle, Daisuke Ishikawa, Alfred Q. R. Baron, Dima Bolmatov, Mikhail Zhernenkov, and Edward R. Lyman