Phase Transition Behaviors And Interactions And Adhesion Of Myelin Lipid Membranes Modulated By Myelin Basic Protein

Abstract

Myelin is a stacked membrane structure that allows for fast, efficient conduction of nerve impulses. It has 8 kinds of lipid molecules on two alternating bilayers and proteins such as myelin basic protein (MBP) which has an important role in maintaining myelin structure. The compact bilayer organization of healthy myelin is believed to require a well-defined range of lipid and protein composition, and lipid-protein interaction. Even though we know that multiple sclerosis (MS) is a morphological transformation involving loss of adhesion between myelin lamellae and sometimes formation of myelin vesicle, its mechanism and causes for demyelination are still under investigation.We have used fluorescence microscopy, Langmuir isotherm, and Langmuir-Blodgett (LB) techniques to investigate how lipid composition of myelin lipid system affects the phase transition behaviors of myelin monolayers and bilayers depending on lateral pressure, temperature, and pH conditions. Model membranes with the composition of the cytoplasmic side of experimental allergic encephalomyelitis (EAE) myelin were also constructed on mica surfaces by LB deposition and the forces between the surfaces measured using the Surface Forces Apparatus (SFA) after exposure to various solution concentrations of MBP.Our findings clearly demonstrate EAE monolayer remains phase-separated under physiological conditions. If the myelin sheath were to form two phases in vivo there are a variety of effects that could result. The line tension between two segregated domains and a local repulsive force could cause the membrane to bulge leading to vesiculation of the membrane. Force-distance measurements between supported myelin bilayers mimicking the cytoplasmic surface of myelin at various surface coverages of MBP indicate that maximum adhesion and minimum cytoplasmic spacing occurs when each negative lipid in the membrane can bind to a positive arginine or lysine group on MBP.