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
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Julio M. Pusterla corresponding
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
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Affiliation as printed
Jülich Centre for Neutron Science (JCNS), Heinz Maier-Leibnitz Zentrum (MLZ), Garching 85748, Germany
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Affiliation as printed
Institut Laue-Langevin (ILL), 71 avenue des Martyrs, CS, 20156, 38042 Grenoble Cedex 9, France
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Affiliation as printed
Institut Laue-Langevin (ILL), 71 avenue des Martyrs, CS, 20156, 38042 Grenoble Cedex 9, France
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Rutherford Appleton Laboratory · ISIS Neutron and Muon Source
Affiliation as printed
ISIS Neutron and Muon Source, Rutherford Appleton Laboratory, Didcot OX11 0QX, United Kingdom
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Rutherford Appleton Laboratory · ISIS Neutron and Muon Source
Affiliation as printed
ISIS Neutron and Muon Source, Rutherford Appleton Laboratory, Didcot OX11 0QX, United Kingdom
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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
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Affiliation as printed
Jülich Centre for Neutron Science (JCNS-1), Forschungszentrum Jülich GmbH, Leo-Brandt Straße, 52428 Jülich, Germany
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Affiliation as printed
Institute of Biological Information Processing (IBI), Mechanobiology (IBI-2), Forschungszentrum Jülich GmbH, Leo Brandt Straße, 52428 Jülich, Germany
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Affiliation as printed
Institute of Biological Information Processing (IBI), Mechanobiology (IBI-2), Forschungszentrum Jülich GmbH, Leo Brandt Straße, 52428 Jülich, Germany
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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
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Affiliation as printed
Jülich Centre for Neutron Science (JCNS-1), Forschungszentrum Jülich GmbH, Leo-Brandt Straße, 52428 Jülich, Germany
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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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