%0 Journal Article
%T Lipid Phase Asymmetry in Mammalian Bilayer Membranes
%J -
%D 2019
%R https://doi.org/10.1016/j.bpj.2018.11.1236
%X Cells invest significant energy to maintain a compositional asymmetry between the two apposing leaflets of the plasma membrane (PM), emphasizing the importance of this distribution for cell homeostasis. Despite the central involvement of PM asymmetry in various physiological processes, the distinct, detailed, comprehensive compositions of the PM leaflets are not known, nor is the influence of asymmetric lipid distribution on leaflet biophysical properties. We therefore combined a detailed lipidomic analysis of PM leaflet compositions with an investigation of leaflet-specific biophysical properties through microinjection of an environment sensitive probe. We further explored if leaflet properties are maintained in intracellular organelles, and the consequences of these asymmetries on the structure of transmembrane proteins. In plasma membranes of human red blood cells, we discovered a dramatic disparity in lipid acyl chains, with the inner leaflet containing approximately two-fold more acyl chain unsaturations compared to the outer leaflet. Membranes containing highly unsaturated lipids are typically characterized by reduced lipid packing and we indeed observed that the inner leaflet was much more disordered than the outer leaflet. This lipid phase asymmetry with the outer leaflet comparable to a liquid ordered ¡°raft¡± phase was largely maintained during endocytosis. An analysis of the human proteome revealed that transmembrane proteins have asymmetric shape in their transmembrane domains in organelles which participate in exo- or endocytosis. This asymmetric shape produces an energetically favourable interaction with the asymmetrically packed membranes, and we conclude that those shapes have co-evolved with the lipid phase asymmetries. The function of the observed phase asymmetry remains to be definitively determined, but we speculate that this arrangement is a ¡°best of both worlds¡±, combining low permeability and high mechanical robustness in the exoplasmic leaflet with high mobility and diffusion in the cytoplasmic leaflet required for dynamic intracellular signalling
%U https://www.cell.com/biophysj/fulltext/S0006-3495(18)32501-3