Physical insights on the self-assembly of myelin sheaths: what drives healthy lamellar stacks to disrupted inverted hexagonal phase*

Myelin sheath is a multilamellar complex of various lipids and proteins that surrounds axons and acts as an insulating layer for proper nerve conduction. In multiple sclerosis (MS), the myelin structure is disrupted impairing its function. Previous studies showed that MS is correlated with a small lipid composition variation and a reduction in the adhesive myelin basic protein (MBP). We show that such alterations result in structural instabilities and phase transition from a lamellar to inverted hexagonal phase, in accordance with pathological in vivo studies. Moreover, alteration in local environmental conditions, such as elevated salinity and temperature, drive the myelin system further into the inverted hexagonal phase [2]. Finally, we will demonstrate that the self-assembly of such complex system presents ion-specific structural modulation that is physiologically relevant. Since the etiology and recovery pathways of MS are currently unclear, these findings delineate novel functional roles to dominant constituents in cytoplasmic myelin sheaths.
[1] R. Shaharabani, et al. JACS 138 (2016) 12159.
[2] R. Shaharabani, et al. PNAS (2018); DOI: 10.1073/pnas.1804275115