Polymer Mediated Interactions Between Myelin Lipid Bilayers

Abstract

The axons of the central nervous system are covered by a multi-layered membrane which provides insulation and high electric signal conductivity to the axons. Swelling of the myelin sheaths is the hallmark of many neurological degenerative diseases like multiple sclerosis. Loss of the myelin membrane involves subtle changes in the interaction forces that hold the membrane stack together. These interaction forces are believed to have more than one origin, the major one arising from the dedicated protein -myelin basic protein (MBP) - which binds to, and bridges, the cytoplasmic sides of myelin membrane via electrostatic and hydrophobic interactions. It has been shown that deimination of MBP leads to a loss of adhesion between myelin membranes and ultimately to swelling of myelin. In the present study, we explored a new strategy that makes use of structured polymers to reverse the effects of loss of adhesion between myelin membranes. By controlling the chemical composition and architecture of the polymers, our results show that it is possible to enhance the adhesion between the membranes using different types of interaction forces like electrostatic forces, depletion forces, bridging forces or combinations of them. Neutral triblock copolymers with a central hydrophobic segment present a strong affinity to the bilayers and enhance the adhesive interaction forces between the membranes via a depletion mechanism similar to hydrophilic homopolymers (like PEG). On the other hand, triblocks copolymers with two hydrophobic lateral blocks promote adhesion between bilayers via bridging interaction controlled by the concentration and segments chain length of the polymer. The results pave a new route to the development of treatments for this debilitating disease and shed a new light on the relationship between polymer structure, self assembly and interactions with complex biomembranes.