Journal Article

FZJ-2020-04116

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Membrane stiffness and myelin basic protein binding strength as molecular origin of multiple sclerosis

Krugmann, B.FZJ* ; Radulescu, A.FZJ* ; Appavou, M.-S.FZJ* ; Koutsioumpas, A.FZJ* ; Stingaciu, L. R. ; Dulle, M.FZJ* ; Förster, S.FZJ* ; Stadler, A. M. (Corresponding author)FZJ*

2020
Macmillan Publishers Limited, part of Springer Nature [London]

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Please use a persistent id in citations: http://hdl.handle.net/2128/25947  doi:10.1038/s41598-020-73671-3

Abstract: Myelin basic protein (MBP) and its interaction with lipids of the myelin sheath plays an important part in the pathology of multiple sclerosis (MS). Previous studies observed that changes in the myelin lipid composition lead to instabilities and enhanced local curvature of MBP-lipid multilayer structures. We investigated the molecular origin of the instability and found that the diseased lipid membrane has a 25% lower bending rigidity, thus destabilizing smooth >1µm curvature radius structures such as in giant unilamellar vesicles. MBP-mediated assembling of lipid bilayers proceeds in two steps, with a slow second step occurring over many days where native lipid membranes assemble into well-defined multilayer structures, whereas diseased lipid membranes form folded assemblies with high local curvature. For both native and diseased lipid mixtures we find that MBP forms dense liquid phases on top of the lipid membranes mediating attractive membrane interactions. Furthermore, we observe MBP to insert into its bilayer leaflet side in case of the diseased lipid mixture, whereas there is no insertion for the native mixture. Insertion increases the local membrane curvature, and could be caused by a decrease of the sphingomyelin content of the diseased lipid mixture. These findings can help to open a pathway to remyelination strategies.

Keyword(s): Health and Life (1st) ; Biology (2nd) ; Soft Condensed Matter (2nd)

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Contributing Institute(s):

1. JCNS-FRM-II (JCNS-FRM-II)
2. Neutronenstreuung (JCNS-1)
3. Heinz Maier-Leibnitz Zentrum (MLZ)

Research Program(s):

1. 6G4 - Jülich Centre for Neutron Research (JCNS) (POF3-623) (POF3-623)
2. 6G15 - FRM II / MLZ (POF3-6G15) (POF3-6G15)
3. 6215 - Soft Matter, Health and Life Sciences (POF3-621) (POF3-621)

Experiment(s):

1. KWS-2: Small angle scattering diffractometer (NL3ao)
2. MARIA: Magnetic reflectometer with high incident angle (NL5N)
3. SNS-NSE: Neutron Spin Echo Spectrometer
4. TEM-MLZ: Transmission electron microscope at MLZ

Appears in the scientific report 2020

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