National Academy of Sciences, Proceedings of the National Academy of Sciences, 9(117), p. 4749-4757, 2020
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Significance Although it is believed that the raft formation in a cell membrane is governed by a selective interaction of different lipids and proteins, mechanisms driving and regulating the lateral membrane heterogeneity remain poorly understood. Here, using multicomponent lipid mixtures and inelastic X-ray scattering, we provide a spatial–temporal window to study lipid–lipid interactions. We show experimental evidence for the formation of dynamic lipid pairs, which are subnanometer in size and have a subnanosecond lifetime. These pairs form transient nanoscopic substructures in the liquid-ordered phase. The presented approach to study membrane heterogeneity is universal and can be applied to more realistic lipid mixtures, offering the possibility to discern differences between the structures of ordered and disordered phases in a cell membrane.