title: Structural Transition in Myelin Membrane as Initiator of Multiple Sclerosis.
abstract: In demyelinating diseases such as multiple sclerosis, disrupted myelin structures impair the functional role of the sheath as an insulating layer for proper nerve conduction. Though the etiology and recovery pathways remain unclear, in vivo studies show alterations in the lipid and the adhesive protein (myelin basic protein, MBP) composition. We find that in vitro cytoplasmic myelin membranes with modified lipid composition and low MBP concentration, as in demyelinating disease, show structural instabilities and pathological phase transition from a lamellar to inverted hexagonal, which involve enhanced local curvature. Similar curvatures are also found in vivo in diseased myelin sheaths. In addition, MBP dimers form a correlated mesh-like network within the inner membrane space, only in the vicinity of native lipid composition. These findings delineate the distinct functional roles of dominant constituents in cytoplasmic myelin sheaths, and shed new light on mechanisms disrupting lipid-protein complexes in the diseased state.
authors.affiliation: Raymond & Beverly Sackler School of Chemistry, Tel Aviv University , Tel Aviv 6997801, Israel.|Tel Aviv University Center for Nanoscience and Nanotechnology, Tel Aviv University , Tel Aviv 6997801, Israel.
authors.forename: Rona
authors.initials: R
authors.lastname: Shaharabani
authors.affiliation: Department of Chemical Engineering and the Russell Berrie Nanotechnology Institute (RBNI), Technion-Israel Institute of Technology , Haifa 3200003, Israel.
authors.forename: Maor
authors.initials: M
authors.lastname: Ram-On
authors.affiliation: Tel Aviv University Center for Nanoscience and Nanotechnology, Tel Aviv University , Tel Aviv 6997801, Israel.|Raymond & Beverly Sackler School of Physics & Astronomy, Tel Aviv University , Tel Aviv 6997801, Israel.
authors.forename: Ram
authors.initials: R
authors.lastname: Avinery
authors.affiliation: Department of Immunology, The Weizmann Institute of Science , Rehovot 7610001, Israel.
authors.forename: Rina
authors.initials: R
authors.lastname: Aharoni
authors.affiliation: Department of Immunology, The Weizmann Institute of Science , Rehovot 7610001, Israel.
authors.forename: Ruth
authors.initials: R
authors.lastname: Arnon
authors.affiliation: Department of Chemical Engineering and the Russell Berrie Nanotechnology Institute (RBNI), Technion-Israel Institute of Technology , Haifa 3200003, Israel.
authors.forename: Yeshayahu
authors.initials: Y
authors.lastname: Talmon
authors.affiliation: Tel Aviv University Center for Nanoscience and Nanotechnology, Tel Aviv University , Tel Aviv 6997801, Israel.|Raymond & Beverly Sackler School of Physics & Astronomy, Tel Aviv University , Tel Aviv 6997801, Israel.|Sagol School of Neuroscience, Tel Aviv University , Tel Aviv 6997801, Israel.
authors.forename: Roy
authors.initials: R
authors.lastname: Beck
mesh_terms: D002462:Cell Membrane / Q000737:chemistry / Q000502:physiology*; D020285:Cryoelectron Microscopy / Q000379:methods; D006801:Humans; D008055:Lipids / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D008956:Models, Chemical; D009103:Multiple Sclerosis / Q000209:etiology*; D009186:Myelin Sheath / Q000737:chemistry / Q000502:physiology*; D014961:X-Ray Diffraction
chemical_list: D008055:Lipids