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Myelin basic protein binding is modulated by leaflet asymmetry and lipid composition

Journal of Colloid and Interface Science, vol. 724, pp. 141116

Abstract

Compositional asymmetry between lipid bilayer leaflets is a defining feature of biological membranes and can modulate protein binding. Here, we investigate how leaflet-specific composition affects the interaction between Myelin Basic Protein and biomimetic myelin membranes using neutron reflectometry. Asymmetric supported myelin bilayers containing deuterated cholesterol in the cytoplasmic leaflet enabled resolution of structural asymmetry. Neutron reflectometry measurements show that Myelin Basic Protein binds preferentially to asymmetric supported bilayers mimicking native myelin, whereas Experimental Autoimmune Encephalomyelitis-modified compositions exhibit weaker binding and more pronounced protein insertion. Disruption of asymmetry-either by thermally induced lipid redistribution or by using symmetric cytoplasmic myelin-leads to a marked reduction in Myelin Basic Protein binding, despite increased membrane charge. Following vesicle adsorption and formation of a second bilayer, the protein layer narrows to near in vivo thickness in both systems, with the diseased condition exhibiting a wider inter-bilayer spacing. These results underscore the relevance of lipid asymmetry and composition in governing protein-membrane interactions, with implications for the molecular basis of myelin stability and demyelination.

Authors 13

  1. Julio M. Pusterla corresponding

    Forschungszentrum Jülich

    Affiliation as printed

    Jülich Centre for Neutron Science (JCNS-1), Forschungszentrum Jülich GmbH, Leo-Brandt Straße, 52428 Jülich, Germany. Electronic address: j.pusterla@fz-juelich.de

  2. Heinz Maier-Leibnitz Zentrum

    Affiliation as printed

    Jülich Centre for Neutron Science (JCNS), Heinz Maier-Leibnitz Zentrum (MLZ), Garching 85748, Germany

  3. Institut Laue-Langevin

    Affiliation as printed

    Institut Laue-Langevin (ILL), 71 avenue des Martyrs, CS, 20156, 38042 Grenoble Cedex 9, France

  4. Institut Laue-Langevin

    Affiliation as printed

    Institut Laue-Langevin (ILL), 71 avenue des Martyrs, CS, 20156, 38042 Grenoble Cedex 9, France

  5. Rutherford Appleton Laboratory · ISIS Neutron and Muon Source

    Affiliation as printed

    ISIS Neutron and Muon Source, Rutherford Appleton Laboratory, Didcot OX11 0QX, United Kingdom

  6. Rutherford Appleton Laboratory · ISIS Neutron and Muon Source

    Affiliation as printed

    ISIS Neutron and Muon Source, Rutherford Appleton Laboratory, Didcot OX11 0QX, United Kingdom

  7. Forschungszentrum Jülich · RWTH Aachen University

    Affiliation as printed

    Jülich Centre for Neutron Science (JCNS-1), Forschungszentrum Jülich GmbH, Leo-Brandt Straße, 52428 Jülich, Germany; Institute of Physical Chemistry, RWTH Aachen University, Landoltweg 2, 52056 Aachen, Germany

  8. Forschungszentrum Jülich

    Affiliation as printed

    Jülich Centre for Neutron Science (JCNS-1), Forschungszentrum Jülich GmbH, Leo-Brandt Straße, 52428 Jülich, Germany

  9. Forschungszentrum Jülich

    Affiliation as printed

    Institute of Biological Information Processing (IBI), Mechanobiology (IBI-2), Forschungszentrum Jülich GmbH, Leo Brandt Straße, 52428 Jülich, Germany

  10. Forschungszentrum Jülich

    Affiliation as printed

    Institute of Biological Information Processing (IBI), Mechanobiology (IBI-2), Forschungszentrum Jülich GmbH, Leo Brandt Straße, 52428 Jülich, Germany

  11. Australian Nuclear Science and Technology Organisation · National Deuteration Facility

    Affiliation as printed

    Australian Nuclear Science and Technology Organisation, National Deuteration Facility, New Illawarra Rd, Lucas Heights, New South Wales, Australia

  12. Forschungszentrum Jülich

    Affiliation as printed

    Jülich Centre for Neutron Science (JCNS-1), Forschungszentrum Jülich GmbH, Leo-Brandt Straße, 52428 Jülich, Germany

  13. Forschungszentrum Jülich · RWTH Aachen University

    Affiliation as printed

    Jülich Centre for Neutron Science (JCNS-1), Forschungszentrum Jülich GmbH, Leo-Brandt Straße, 52428 Jülich, Germany; Institute of Physical Chemistry, RWTH Aachen University, Landoltweg 2, 52056 Aachen, Germany. Electronic address: a.stadler@fz-juelich.de

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References 71