We offer to your attention an article published in the PNAS journal (Proceedings of the National Academy of Sciences of the United States of America). The article is devoted to the study of picosecond dynamics of lipid molecules in multicomponent membranes using the method of inelastic x-ray scattering with high resolution on the transmitted energy. The experiments were carried out on spectrometers of the European Synchrotron Radiation Facility (France) and the Spring8 synchrotron (Japan). The work was performed by an international team of scientists from the Brookhaven National Laboratory (USA), the Laboratory of Neutron Physics JINR (D. Soloviov and K. Zhernenkov), the University of Tennessee (USA), and Volgograd National Technical University (Russia).

Functional lipid pairs as building blocks of phase-separated membranes

Authors: Dmytro Soloviov, Yong Q. Cai, Dima Bolmatov, Alexey Suvorov, Kirill Zhernenkov, Dmitry Zav’yalov, Alexey Bosak, Hiroshi Uchiyama, and Mikhail Zhernenkov

Biological membranes exhibit a great deal of compositional and phase heterogeneity due to hundreds of chemically distinct components. As a result, phase separation processes in cell membranes are extremely difficult to study, especially at the molecular level. It is currently believed that the lateral membrane heterogeneity and the formation of domains, or rafts, are driven by lipid–lipid and lipid–protein interactions. Nevertheless, the underlying mechanisms regulating membrane heterogeneity remain poorly understood. In the present work, we combine inelastic X-ray scattering with molecular dynamics simulations to provide direct evidence for the existence of strongly coupled transient lipid pairs. These lipid pairs manifest themselves experimentally through optical vibrational (a.k.a. phononic) modes observed in binary (1,2-dipalmitoyl-sn-glycero-3-phosphocholine [DPPC]–cholesterol) and ternary (DPPC–1,2-dioleoyl-sn-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-glycero-3-phosphocholine [DOPC/POPC]–cholesterol) systems. The existence of a phononic gap in these vibrational modes is a direct result of the finite size of patches formed by these lipid pairs. The observation of lipid pairs provides a spatial (subnanometer) and temporal (subnanosecond) window into the lipid–lipid interactions in complex mixtures of saturated/unsaturated lipids and cholesterol. Our findings represent a step toward understanding the lateral organization and dynamics of membrane domains using a well-validated probe with a high spatial and temporal resolution.

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