Transbilayer lipid interactions mediate nanoclustering of lipid-anchored proteins

Riya Raghupathy, Anupama Ambika Anilkumar, Anirban Polley, Parvinder Pal Singh, Mahipal Yadav, Charles Johnson, Sharad Suryawanshi, Varma Saikam, Sanghapal D. Sawant, Aniruddha Panda, Zhongwu Guo, Ram A. Vishwakarma, Madan Rao, Satyajit Mayor

    Research output: Contribution to journalArticleScientificpeer-review

    177 Citations (Scopus)


    Understanding how functional lipid domains in live cell membranes are generated has posed a challenge. Here, we show that transbilayer interactions are necessary for the generation of cholesterol-dependent nanoclusters of GPI-anchored proteins mediated by membrane-adjacent dynamic actin filaments. We find that long saturated acyl-chains are required for forming GPI-anchor nanoclusters. Simultaneously, at the inner leaflet, long acyl-chain-containing phosphatidylserine (PS) is necessary for transbilayer coupling. All-atom molecular dynamics simulations of asymmetric multicomponent-membrane bilayers in a mixed phase provide evidence that immobilization of long saturated acyl-chain lipids at either leaflet stabilizes cholesterol-dependent transbilayer interactions forming local domains with characteristics similar to a liquid-ordered (lo) phase. This is verified by experiments wherein immobilization of long acyl-chain lipids at one leaflet effects transbilayer interactions of corresponding lipids at the opposite leaflet. This suggests a general mechanism for the generation and stabilization of nanoscale cholesterol-dependent and actin-mediated lipid clusters in live cell membranes.

    Original languageEnglish
    Pages (from-to)581-594
    Number of pages14
    Issue number3
    Publication statusPublished - 23 Apr 2015
    Publication typeA1 Journal article-refereed

    Publication forum classification

    • Publication forum level 3

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Medicine(all)


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