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@ARTICLE{Krugmann:885825,
author = {Krugmann, Benjamin and Radulescu, Aurel and Appavou,
Marie-Sousai and Koutsioumpas, Alexandros and Stingaciu,
Laura R. and Dulle, Martin and Förster, Stephan and
Stadler, Andreas M.},
title = {{M}embrane stiffness and myelin basic protein binding
strength as molecular origin of multiple sclerosis},
journal = {Scientific reports},
volume = {10},
number = {1},
issn = {2045-2322},
address = {[London]},
publisher = {Macmillan Publishers Limited, part of Springer Nature},
reportid = {FZJ-2020-04116},
pages = {16691},
year = {2020},
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.},
cin = {JCNS-FRM-II / JCNS-1 / MLZ},
ddc = {600},
cid = {I:(DE-Juel1)JCNS-FRM-II-20110218 /
I:(DE-Juel1)JCNS-1-20110106 / I:(DE-588b)4597118-3},
pnm = {6G4 - Jülich Centre for Neutron Research (JCNS) (POF3-623)
/ 6G15 - FRM II / MLZ (POF3-6G15) / 6215 - Soft Matter,
Health and Life Sciences (POF3-621)},
pid = {G:(DE-HGF)POF3-6G4 / G:(DE-HGF)POF3-6G15 /
G:(DE-HGF)POF3-6215},
experiment = {EXP:(DE-MLZ)KWS2-20140101 / EXP:(DE-MLZ)MARIA-20140101 /
EXP:(DE-Juel1)SNS-NSE-20150203 /
EXP:(DE-MLZ)TEM-MLZ-20151210},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33028889},
UT = {WOS:000577449800036},
doi = {10.1038/s41598-020-73671-3},
url = {https://juser.fz-juelich.de/record/885825},
}