Membrane stiffness and myelin basic protein binding strength as molecular origin of multiple sclerosis.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
07 10 2020
07 10 2020
Historique:
received:
22
06
2020
accepted:
21
09
2020
entrez:
8
10
2020
pubmed:
9
10
2020
medline:
2
1
2021
Statut:
epublish
Résumé
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]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.
Identifiants
pubmed: 33028889
doi: 10.1038/s41598-020-73671-3
pii: 10.1038/s41598-020-73671-3
pmc: PMC7542173
doi:
Substances chimiques
Lipid Bilayers
0
Liposomes
0
Myelin Basic Protein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
16691Références
Purves, D. et al. Increased Conduction Velocity as a Result of Myelination, chap. 2 (Sinauer Associates, USA, 2001).
Quarles, R. H., Macklin, W. B. & Morell, P. Myelin formation, structure and biochemistry, chap. 4, 51–71 (Academic Press, 2006), 7 edn.
Boggs, J. M. Myelin basic protein: a multifunctional protein. Cell. Mol. Life Sci. 63, 1945–1961. https://doi.org/10.1007/s00018-006-6094-7 (2006).
doi: 10.1007/s00018-006-6094-7
pubmed: 16794783
Stollery, J. G. & Vail, W. J. Interactions of divalent cations or basic proteins with phosphatidylethanolamine vesicles. Biochim. Biophys. Acta 471, 372–390, https://doi.org/10.1016/0005-2736(77)90043-8 (1977).
Lampe, P. D. & Nelsestuen, G. L. Myelin basic protein-enhanced fusion of membranes. Biochimica et Biophysica Acta (BBA) - Biomembranes 693, 320–325. https://doi.org/10.1016/0005-2736(82)90438-2 (1982).
doi: 10.1016/0005-2736(82)90438-2
Lampe, P. D., Wei, G. J. & Nelsestuen, G. L. Stopped-flow studies of myelin basic protein association with phospholipid vesicles and subsequent vesicle aggregation. Biochemistry 22, 1594–1599. https://doi.org/10.1021/bi00276a011 (1983).
doi: 10.1021/bi00276a011
pubmed: 6189513
Maggio, B. & Yu, R. K. Interaction and fusion of unilamellar vesicles containing cerebrosides and sulfatides induced by myelin basic protein. Chem. Phys. Lipids 51, 127–136. https://doi.org/10.1016/0009-3084(89)90046-7 (1989).
doi: 10.1016/0009-3084(89)90046-7
pubmed: 2480186
Haas, H. et al. Myelin model membranes on solid substrates. Thin Solid Films 327–329, 627–631. https://doi.org/10.1016/S0040-6090(98)00727-5 (1998).
doi: 10.1016/S0040-6090(98)00727-5
Polverini, E. et al. Interaction of myelin basic protein with phospholipid monolayers: Mechanism of protein penetration. Langmuir 19, 872–877. https://doi.org/10.1021/la020801a (2003).
doi: 10.1021/la020801a
Haas, H. et al. Laminar order within langmuir-blodgett multilayers from phospholipid and myelin basic protein: A neutron reflectivity study. Langmuir 23, 8491–8496. https://doi.org/10.1021/la700733y (2007).
doi: 10.1021/la700733y
pubmed: 17616158
Shen, Y., Saboe, P. O., Sines, I. T., Erbakan, M. & Kumar, M. Biomimetic membranes: a review. J. Membr. Sci. 454, 359–381. https://doi.org/10.1016/j.memsci.2013.12.019 (2014).
doi: 10.1016/j.memsci.2013.12.019
Marquardt, D., Geier, B. & Pabst, G. Asymmetric lipid membranes: towards more realistic model systems. Membranes 5, 180–196. https://doi.org/10.3390/membranes5020180 (2015).
doi: 10.3390/membranes5020180
pubmed: 25955841
pmcid: 4496639
Heberle, F. A. et al. Subnanometer structure of an asymmetric model membrane: interleaflet coupling influences domain properties. Langmuir 32, 5195–5200 (2016).
doi: 10.1021/acs.langmuir.5b04562
Shaharabani, R. et al. Structural transition in myelin membrane as initiator of multiple sclerosis. Journal of the American Chemical Society 138, 12159–12165. https://doi.org/10.1021/jacs.6b04826 (2016). PMID: 27548321.
Eicher, B. et al. Joint small-angle X-ray and neutron scattering data analysis of asymmetric lipid vesicles. Journal of Applied Crystallography 50, 419–429. https://doi.org/10.1107/S1600576717000656 (2017).
doi: 10.1107/S1600576717000656
pubmed: 28381971
pmcid: 5377341
Eicher, B. et al. Intrinsic curvature-mediated transbilayer coupling in asymmetric lipid vesicles. Biophys. J. 114, 146–157 (2018).
doi: 10.1016/j.bpj.2017.11.009
Shaharabani, R., Ram-On, M., Talmon, Y. & Beck, R. Pathological transitions in myelin membranes driven by environmental and multiple sclerosis conditions. Proceedings of the National Academy of Sciences 115, 11156–11161, https://doi.org/10.1073/pnas.1804275115 (2018). https://www.pnas.org/content/115/44/11156.full.pdf .
Min, Y. et al. Interaction forces and adhesion of supported myelin lipid bilayers modulated by myelin basic protein. Proc. Natl. Acad. Sci. 106, 3154–3159, https://doi.org/10.1073/pnas.0813110106 , http://www.pnas.org/content/106/9/3154.full.pdf (2009).
Min, Y. et al. Critical and off-critical miscibility transitions in model extracellular and cytoplasmic myelin lipid monolayers. Biophys. J. 100, 1490–1498. https://doi.org/10.1016/j.bpj.2011.02.009 (2011).
doi: 10.1016/j.bpj.2011.02.009
pubmed: 21402031
pmcid: 3059582
Raasakka, A. et al. Membrane association landscape of myelin basic protein portrays formation of the myelin major dense line. Sci. Rep. 7, 4974. https://doi.org/10.1038/s41598-017-05364-3 (2017).
doi: 10.1038/s41598-017-05364-3
pubmed: 28694532
pmcid: 5504075
Radulescu, A., Szekely, N. K. & Appavou, M.-S. Kws-2: Small angle scattering diffractometer. Journal of large-scale research facilities JLSRF 1, 29. https://doi.org/10.1016/j.nima.2012.06.027 (2015).
doi: 10.1016/j.nima.2012.06.027
David, G. & Pérez, J. Combined sampler robot and high-performance liquid chromatography: a fully automated system for biological small-angle X-ray scattering experiments at the Synchrotron SOLEIL SWING beamline. J. Appl. Crystallogr. 42, 892–900. https://doi.org/10.1107/S0021889809029288 (2009).
doi: 10.1107/S0021889809029288
Boggs, J. M. & Moscarello, M. A. Effect of basic protein from human central nervous system myelin on lipid bilayer structure. The Journal of Membrane Biology 39, 75–96. https://doi.org/10.1007/BF01872756 (1978).
doi: 10.1007/BF01872756
pubmed: 204786
Helfrich, W. & Kozlov, M. Bending tensions and the bending rigidity of fluid membranes. J. Phys. II(3), 287–292 (1993).
Arriaga, L. R. et al. Stiffening effect of cholesterol on disordered lipid phases: a combined neutron spin echo+ dynamic light scattering analysis of the bending elasticity of large unilamellar vesicles. Biophysical journal 96, 3629–3637 (2009).
doi: 10.1016/j.bpj.2009.01.045
Woodka, A. C., Butler, P. D., Porcar, L., Farago, B. & Nagao, M. Lipid bilayers and membrane dynamics: insight into thickness fluctuations. Phys. Rev. Lett. 109, 058102 (2012).
doi: 10.1103/PhysRevLett.109.058102
Nickels, J. D. et al. Mechanical properties of nanoscopic lipid domains. Journal of the American Chemical Society 137, 15772–15780 (2015).
doi: 10.1021/jacs.5b08894
Zilman, A. & Granek, R. Undulations and dynamic structure factor of membranes. Phys. Rev. Lett. 77, 4788 (1996).
doi: 10.1103/PhysRevLett.77.4788
Watson, M. C. & Brown, F. L. Interpreting membrane scattering experiments at the mesoscale: the contribution of dissipation within the bilayer. Biophysical journal 98, L9–L11 (2010).
doi: 10.1016/j.bpj.2009.11.026
Takeda, T. et al. Neutron spin-echo investigations of membrane undulations in complex fluids involving amphiphiles. J. Phys. Chem. Solids 60, 1375–1377. https://doi.org/10.1016/S0022-3697(99)00122-5 (1999).
doi: 10.1016/S0022-3697(99)00122-5
Farago, B., Monkenbusch, M., Goecking, K., Richter, D. & Huang, J. Dynamics of microemulsions as seen by neutron spin echo. Physica B: Condensed Matter 213, 712–717 (1995).
doi: 10.1016/0921-4526(95)00257-A
Martinez, G. V., Dykstra, E. M., Lope-Piedrafita, S., Job, C. & Brown, M. F. Nmr elastometry of fluid membranes in the mesoscopic regime. Phys. Rev. E 66, 050902 (2002).
doi: 10.1103/PhysRevE.66.050902
Rondelli, V. et al. Amyloid-[Formula: see text] peptides in interaction with raft-mime model membranes: a neutron reflectivity insight. Sci. Rep. 6, 20997. https://doi.org/10.1038/srep20997 (2016).
doi: 10.1038/srep20997
pubmed: 26880066
pmcid: 4754687
Colombo, L. et al. Pathogenic a[Formula: see text] a2v versus protective a[Formula: see text] a2t mutation: Early stage aggregation and membrane interaction. Biophysical Chemistry 229, 11 – 18, https://doi.org/10.1016/j.bpc.2017.05.001 (2017). SIBPA 2016 - XXIII SIBPA Congress.
Pfefferkorn, C. M. et al. Depth of [Formula: see text]-synuclein in a bilayer determined by fluorescence, neutron reflectometry, and computation. Biophys. J. 102, 613–621. https://doi.org/10.1016/j.bpj.2011.12.051 (2012).
doi: 10.1016/j.bpj.2011.12.051
pubmed: 22325285
pmcid: 3274814
Mattauch, S. et al. The high-intensity reflectometer of the Jülich Centre for Neutron Science: MARIA. J. Appl. Crystallogr. 51, 646–654. https://doi.org/10.1107/S1600576718006994 (2018).
doi: 10.1107/S1600576718006994
pubmed: 29896056
pmcid: 5988004
Marsh, D. Liquid-ordered phases induced by cholesterol: A compendium of binary phase diagrams. Biochimica et Biophysica Acta (BBA) - Biomembranes 1798, 688–699. https://doi.org/10.1016/j.bbamem.2009.12.027 (2010).
doi: 10.1016/j.bbamem.2009.12.027
Nelson, A. Co-refinement of multiple-contrast neutron/X-ray reflectivity data using MOTOFIT. J. Appl. Crystallogr. 39, 273–276. https://doi.org/10.1107/S0021889806005073 (2006).
doi: 10.1107/S0021889806005073
Raine, C. S. Morphology of myelin and myelination. In Myelin 1–50 (Springer, 1984).
Aggarwal, S. et al. Myelin membrane assembly is driven by a phase transition of myelin basic proteins into a cohesive protein meshwork. PLoS Biol. 11, (2013).
Bakhti, M., Aggarwal, S. & Simons, M. Myelin architecture: zippering membranes tightly together. Cellular and molecular life sciences 71, 1265–1277 (2014).
doi: 10.1007/s00018-013-1492-0
Kattnig, D. R., Bund, T., Boggs, J. M., Harauz, G. & Hinderberger, D. Lateral self-assembly of 18.5-kda myelin basic protein (mbp) charge component-c1 on membranes. Biochim. Biophys. Acta 1818, 2636–2647 (2012).
Beniac, D. R. et al. Three-dimensional structure of myelin basic protein i. reconstruction via angular reconstitution of randomly oriented single particles. J. Biol. Chem. 272, 4261–4268 (1997).
Xu, H. et al. Orientation of a monoclonal antibody adsorbed at the solid/solution interface: a combined study using atomic force microscopy and neutron reflectivity. Langmuir 22, 6313–6320 (2006).
doi: 10.1021/la0532454
Stadler, A. M. et al. Internal nanosecond dynamics in the intrinsically disordered myelin basic protein. J. Am. Chem. Soc. 136, 6987–6994. https://doi.org/10.1021/ja502343b (2014).
doi: 10.1021/ja502343b
pubmed: 24758710
Ohl, M. et al. The spin-echo spectrometer at the spallation neutron source (sns). Nucl. Instrum. Methods Phys. Res. 696, 85–99. https://doi.org/10.1016/j.nima.2012.08.059 (2012).
doi: 10.1016/j.nima.2012.08.059