Solubilization of lipids and lipid phases by the styrene-maleic acid copolymer

Juan J Dominguez Pardo, Jonas M Dörr, Aditya Iyer, Ruud C Cox, Stefan Scheidelaar, Martijn C Koorengevel, Vinod Subramaniam, J Antoinette Killian

    Research output: Contribution to JournalArticleAcademicpeer-review

    Abstract

    A promising tool in membrane research is the use of the styrene-maleic acid (SMA) copolymer to solubilize membranes in the form of nanodiscs. Since membranes are heterogeneous in composition, it is important to know whether SMA thereby has a preference for solubilization of either specific types of lipids or specific bilayer phases. Here, we investigated this by performing partial solubilization of model membranes and analyzing the lipid composition of the solubilized fraction. We found that SMA displays no significant lipid preference in homogeneous binary lipid mixtures in the fluid phase, even when using lipids that by themselves show very different solubilization kinetics. By contrast, in heterogeneous phase-separated bilayers, SMA was found to have a strong preference for solubilization of lipids in the fluid phase as compared to those in either a gel phase or a liquid-ordered phase. Together the results suggest that (1) SMA is a reliable tool to characterize native interactions between membrane constituents, (2) any solubilization preference of SMA is not due to properties of individual lipids but rather due to properties of the membrane or membrane domains in which these lipids reside and (3) exploiting SMA resistance rather than detergent resistance may be an attractive approach for the isolation of ordered domains from biological membranes.

    Original languageEnglish
    Pages (from-to)91-101
    Number of pages11
    JournalEuropean Biophysics Journal
    Volume46
    Issue number1
    DOIs
    Publication statusPublished - Jan 2017

    Funding

    This work was supported financially by NWO Chemical Sciences, ECHO grant (no. 711-013-005) (J.J.D.P) and by the Foundation for Fundamental Research on Matter (FOM), program nos. 126 (S.S.) and 127 (A.I., V.S.) as well as by the Seventh Framework Program of the European Union (Initial Training Network “ManiFold,” grant 317371) (J.M.D.). We thank M. R. Hogeboom, J. J. Rietveld, R. M. Hopman and H. Keser for optimizing the lipid solubilization parameters. This work used the platforms of the Grenoble Instruct centre (ISBG;UMS 3518 CNRS-CEA-UJF-EMBL) with support from FRISBI (ANR-10-INSB-05-02) and GRAL (ANR-10-LABX-49-01) within the Grenoble partnership for structural biology (PSB). We are very grateful to Dr. C. Moriscot from the Electron Microscopy platform of the Integrated Structural Biology of Grenoble (ISBG, UMI3265) for performing the TEM imaging and to B. W. M. Kuipers from the University of Utrecht for advice and support in DLS analysis.

    FundersFunder number
    Seventh Framework Program of the European Union
    Seventh Framework Programme317371
    Stichting voor Fundamenteel Onderzoek der Materie126, 127
    Nederlandse Organisatie voor Wetenschappelijk Onderzoek711-013-005

      Keywords

      • Cell Membrane
      • Journal Article
      • Lipid Bilayers
      • Maleates
      • Polystyrenes
      • Solubility

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