The myelin sheath, a repeating multilamellar stack of lipid-protein complex, acts as an electrical insulator, forming a capacitor surrounding the axon of the nervous system. The lipids and protein ratio found in-vivo are assumed to play a critical role in determining the structure of the myelin layers. In neurodegenerative diseases, such as multiple sclerosis (MS), demyelination is attributed to alterations in lipid composition and to decreased concentration of myelin basic protein, the key protein in myelin sheaths.

In order to model and understand the development of MS from a biophysical perspective we use synchrotron small X-ray scattering and direct cryogenic transmission electron microscopy. We perform in-vitro structural measurements in model systems mimicking cytoplasmic myelin sheath complexes. We found that such modifications in lipids composition, as in the MS diseased state, result with structural instabilities and pathological phase transition from lamellar to inverted hexagonal phase that involve enhanced local curvature (JACS 2016, 138, 12159). Similar enhanced local curvatures are also found in diseased in-vivo myelin sheaths. Since the etiology and recovery pathways of MS are currently unclear, these findings delineate novel functional roles to dominant constituents in cytoplasmic myelin sheaths, that may shed new light on mechanisms disrupting lipid-protein complexes, and suggest new courses for diagnosis and treatment for MS.