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J Phys Chem Lett. 2018 Sep 20;9(18):5527-5533. doi: 10.1021/acs.jpclett.8b01877. Epub 2018 Sep 11.

Cholesterol Flip-Flop Impacts Domain Registration in Plasma Membrane Models.

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Groningen Biomolecular Sciences and Biotechnology Institute and The Zernike Institute for Advanced Material , University of Groningen , Nijenborgh 7 , 9747 AG Groningen , Netherlands.
Biosciences and Biotechnology Division, Physical and Life Sciences Directorate , Lawrence Livermore National Laboratory , 7000 East Avenue , Livermore , 94550 California , United States.


The plasma membrane is a highly complex multicomponent system that is central to the functioning of cells. Cholesterol, a key lipid component of the plasma membrane, promotes the formation of nanodomains. These nanodomains are often correlated across the two membrane leaflets, but the underlying physical mechanism remains unclear. Using coarse-grained molecular dynamics simulations, we investigate the influence of cholesterol flip-flop on membrane properties, in particular, the interleaflet coupling of cholesterol-enriched domains. We show that the cholesterol density correlation between the leaflets of an average mammalian plasma membrane is significantly reduced by suppressing interleaflet cholesterol population. Our results suggest an amplifying role of cholesterol in signal transduction across the leaflets.

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