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

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

Publication date: Oct 07, 2020

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 [Formula: see text]um 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.

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Concepts Keywords
Bilayer Lamella
Curvature Sphingomyelin
Lipid Biological membrane
Lipid Membrane Membrane curvature
Lipids Myelin
Membrane Lipid bilayer
Multiple Sclerosis Membrane biology
Myelin Branches of biology
Myelin Sheath Unilamellar liposome
Pathology Model lipid bilayer
Sci
Sphingomyelin
Stiffness
Vesicles

Semantics

Type Source Name
disease MESH multiple sclerosis
disease MESH pathology
drug DRUGBANK Coenzyme M
drug DRUGBANK Tretamine
drug DRUGBANK Silicon
disease MESH Neurodegenerative diseases
pathway REACTOME Neurodegenerative Diseases
disease MESH demyelination
drug DRUGBANK Methylergometrine
drug DRUGBANK Cholesterol
disease MESH experimental autoimmune encephalomyelitis
drug DRUGBANK Phosphatidyl serine
disease MESH aging
drug DRUGBANK Albendazole
drug DRUGBANK Water
disease MESH separation
disease MESH growth
drug DRUGBANK DL-dimyristoylphosphatidylcholine
drug DRUGBANK DL-dimyristoylphosphatidylglycerol
drug DRUGBANK Phosphatidylethanolamine
drug DRUGBANK Tricyclazole
drug DRUGBANK Trestolone

Original Article

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