Phonons reveal coupled cholesterol-lipid dynamics in ternary membranes
Date
2024-12-03
Journal Title
Journal ISSN
Volume Title
Publisher
Biophysical Journal
Abstract
Experimental studies of collective dynamics in lipid bilayers have been challenging due to the energy resolution required to observe these low-energy phonon-like modes. However, inelastic x-ray scattering (IXS) measurements—a technique for probing vibrations in soft and biological materials—are now possible with sub-meV resolution, permitting direct observation of low-energy, phonon-like modes in lipid membranes. Here, IXS measurements with sub-meV energy resolution reveal a low-energy optic-like phonon mode at roughly 3 meV in the liquid-ordered ðLoÞ and liquid-disordered phases of a ternary lipid mixture. This mode is only observed experimentally at momentum transfers greater than 5 nm 1 in the Lo system. A similar gapped mode is also observed in all-atom molecular dynamics (MD) simulations of the same mixture, indicating that the simulations accurately represent the fast, collective dynamics in the L o phase. Its optical nature and the Q range of the gap together suggest that the observed mode is due to the coupled motion of cholesterol-lipid pairs, separated by several hydrocarbon chains within the membrane plane. Analysis of the simulations provides molecular insight into the origin of the mode in transient, nanoscale substructures of hexagonally packed hydrocarbon chains. This nanoscale hexagonal packing was previously reported based on MD simulations and, later, by NMR measurements. Here, however, the integration of IXS and MD simulations identifies a new signature of the Lo substructure in the collective lipid dynamics, thanks to the recent confluence of IXS sensitivity and MD simulation capabilities.
Description
This article was originally published in Biophysical Journal. The version of record is available at: https://doi.org/10.1016/j.bpj.2024.10.017.
© 2024 Biophysical Society. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/.
This article will be embargoed until 12/3/2025.
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Citation
Fitzgerald III JE, Soloviov D, Cai YQ, Heberle FA, Ishikawa D, Baron AQR, Bolmatov D, Zhernenkov M, Lyman ER, Phonons reveal coupled cholesterol-lipid dynamics in ternary membranes, Biophysical Journal (2024), doi: https://doi.org/10.1016/j.bpj.2024.10.017.