Forschungszentrum Jülich GmbH, Garching
(Germany). Jülich Centre for Neutron Science at MLZ; RWTH Aachen Univ. (Germany). Inst. of Physical Chemistry; OSTI
Forschungszentrum Jülich GmbH, Garching (Germany). Jülich Centre for Neutron Science at MLZ
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Spallation Neutron Source (SNS)
Forschungszentrum Jülich GmbH, Garching (Germany). Jülich Centre for Neutron Science (JCNS-1). Inst. for Biological Information Processing (IBI-8)
RWTH Aachen Univ. (Germany). Inst. of Physical Chemistry
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.
Krugmann, Benjamin, Radulescu, Aurel, Appavou, Marie-Sousai, Koutsioubas, Alexandros, Stingaciu, Laura R., Dulle, Martin, Förster, Stephan, & Stadler, Andreas M. (2020). Membrane stiffness and myelin basic protein binding strength as molecular origin of multiple sclerosis. Scientific Reports, 10(1). https://doi.org/10.1038/s41598-020-73671-3
@article{osti_1815644,
author = {Krugmann, Benjamin and Radulescu, Aurel and Appavou, Marie-Sousai and Koutsioubas, Alexandros and Stingaciu, Laura R. and Dulle, Martin and Förster, Stephan and Stadler, Andreas M.},
title = {Membrane stiffness and myelin basic protein binding strength as molecular origin of multiple sclerosis},
annote = {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.},
doi = {10.1038/s41598-020-73671-3},
url = {https://www.osti.gov/biblio/1815644},
journal = {Scientific Reports},
issn = {ISSN 2045-2322},
number = {1},
volume = {10},
place = {United States},
publisher = {Nature Publishing Group},
year = {2020},
month = {10}}
Radulescu, Aurel; Pipich, Vitaliy; Ioffe, Alexander
Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, Vol. 689https://doi.org/10.1016/j.nima.2012.06.027
Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, Vol. 696https://doi.org/10.1016/j.nima.2012.08.059