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    Differential effects of lipids and lyso-lipids on the mechanosensitivity of the mechanosensitive channels MscL and MscS

    Access Status
    Open access via publisher
    Authors
    Nomura, T.
    Cranfield, C.
    Deplazes, Evelyne
    Owen, D.
    Macmillan, A.
    Battle, A.
    Constantine, M.
    Sokabe, M.
    Martinac, B.
    Date
    2012
    Type
    Journal Article
    
    Metadata
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    Citation
    Nomura, T. and Cranfield, C. and Deplazes, E. and Owen, D. and Macmillan, A. and Battle, A. and Constantine, M. et al. 2012. Differential effects of lipids and lyso-lipids on the mechanosensitivity of the mechanosensitive channels MscL and MscS. PNAS. 109 (22): pp. 8770-8775.
    Source Title
    PNAS
    DOI
    10.1073/pnas.1200051109
    ISSN
    0027-8424
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/6505
    Collection
    • Curtin Research Publications
    Abstract

    Mechanosensitive (MS) channels of small (MscS) and large (MscL) conductance are the major players in the protection of bacterial cells against hypoosmotic shock. Although a great deal is known about structure and function of these channels, much less is known about how membrane lipids may influence their mechanosensitivity and function. In this study, we use liposome coreconstitution to examine the effects of different types of lipids on MscS and MscL mechanosensitivity simultaneously using the patch-clamp technique and confocal microscopy. Fluorescence lifetime imaging (FLIM)-FRET microscopy demonstrated that coreconstitution of MscS and MscL led to clustering of these channels causing a significant increase in the MscS activation threshold. Furthermore, the MscL/MscS threshold ratio dramatically decreased in thinner compared with thicker bilayers and upon addition of cholesterol, known to affect the bilayer thickness, stiffness and pressure profile. In contrast, application of micromolar concentrations of lysophosphatidylcholine (LPC) led to an increase of the MscL/MscS threshold ratio. These data suggest that differences in hydrophobic mismatch and bilayer stiffness, change in transbilayer pressure profile, and close proximity of MscL and MscS affect the structural dynamics of both channels to a different extent. Our findings may have far-reaching implications for other types of ion channels and membrane proteins that, like MscL and MscS, may coexist in multiple molecular complexes and, consequently, have their activation characteristics significantly affected by changes in the lipid environment and their proximity to each other.

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