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• W2956368086 startingPage "698837" @default.
• W2956368086 abstract "A fundamental feature of cellular plasma membranes (PM) is the asymmetric distribution of lipids between the bilayer leaflets. This asymmetry is central to cellular physiology, regulating signaling, apoptosis, coagulation, and cell-cell fusion. While the broad transbilayer distributions of some lipid types are well established, the detailed lipidomic asymmetry of the PM has not been characterized and thus the compositions of the individual leaflets remain poorly understood. Further, how these compositional differences contribute to structural asymmetries between PM leaflets in living cells is not defined. Here, we report the distinct lipidomes and biophysical properties of both monolayers in living mammalian PMs. Using mass spectrometry coupled to enzymatic digestion, we report the detailed compositions of PM leaflets of human erythrocytes. We find a dramatic asymmetry in phospholipid unsaturation, with the cytoplasmic leaflet being ~2-fold more unsaturated than the exoplasmic. Atomistic simulations of lipid mixtures compiled from the lipidomic observations suggested significant asymmetries in lipid order, packing, and dynamics between the two PM leaflets. These were probed directly in the PM of living cells by Fluorescence Lifetime Imaging Microscopy (FLIM) of leaflet-selective, environment-sensitive probes. The outer PM leaflet is highly packed and ordered, resembling a liquid ordered phase, whereas the inner leaflet is significantly more disordered. This biophysical asymmetry is maintained in the endocytic system. These observations reveal the detailed compositional and biophysical asymmetry of mammalian plasma membranes, elucidating fundamental design principles of living membranes." @default.
• W2956368086 created "2019-07-23" @default.
• W2956368086 creator A5002316926 @default.
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• W2956368086 creator A5044078326 @default.
• W2956368086 creator A5045049371 @default.
• W2956368086 creator A5049584163 @default.
• W2956368086 date "2019-07-11" @default.
• W2956368086 modified "2023-09-24" @default.
• W2956368086 title "The Molecular and Structural Asymmetry of the Plasma Membrane" @default.
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• W2956368086 hasPublicationYear "2019" @default.
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