Membrane stiffness and myelin basic protein binding strength as molecular origin of multiple sclerosis

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 multila...

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Autores principales:	Benjamin Krugmann, Aurel Radulescu, Marie-Sousai Appavou, Alexandros Koutsioubas, Laura R. Stingaciu, Martin Dulle, Stephan Förster, Andreas M. Stadler
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/68c49854c55243a9befe30a3a1366a0e
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spelling	oai:doaj.org-article:68c49854c55243a9befe30a3a1366a0e2021-12-02T18:36:13ZMembrane stiffness and myelin basic protein binding strength as molecular origin of multiple sclerosis10.1038/s41598-020-73671-32045-2322https://doaj.org/article/68c49854c55243a9befe30a3a1366a0e2020-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-73671-3https://doaj.org/toc/2045-2322Abstract 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 $$>1\,$$ > 1 µm 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.Benjamin KrugmannAurel RadulescuMarie-Sousai AppavouAlexandros KoutsioubasLaura R. StingaciuMartin DulleStephan FörsterAndreas M. StadlerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-11 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Benjamin Krugmann Aurel Radulescu Marie-Sousai Appavou Alexandros Koutsioubas Laura R. Stingaciu Martin Dulle Stephan Förster Andreas M. Stadler Membrane stiffness and myelin basic protein binding strength as molecular origin of multiple sclerosis
description	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 $$>1\,$$ > 1 µm 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.
format	article
author	Benjamin Krugmann Aurel Radulescu Marie-Sousai Appavou Alexandros Koutsioubas Laura R. Stingaciu Martin Dulle Stephan Förster Andreas M. Stadler
author_facet	Benjamin Krugmann Aurel Radulescu Marie-Sousai Appavou Alexandros Koutsioubas Laura R. Stingaciu Martin Dulle Stephan Förster Andreas M. Stadler
author_sort	Benjamin Krugmann
title	Membrane stiffness and myelin basic protein binding strength as molecular origin of multiple sclerosis
title_short	Membrane stiffness and myelin basic protein binding strength as molecular origin of multiple sclerosis
title_full	Membrane stiffness and myelin basic protein binding strength as molecular origin of multiple sclerosis
title_fullStr	Membrane stiffness and myelin basic protein binding strength as molecular origin of multiple sclerosis
title_full_unstemmed	Membrane stiffness and myelin basic protein binding strength as molecular origin of multiple sclerosis
title_sort	membrane stiffness and myelin basic protein binding strength as molecular origin of multiple sclerosis
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/68c49854c55243a9befe30a3a1366a0e
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Membrane stiffness and myelin basic protein binding strength as molecular origin of multiple sclerosis

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