Structure of myelin lipid bilayers: Changes during maturation

Abstract

We have studied the structure of oriented multilayers of total myelin lipid using X-ray diffraction and have derived one-dimensional electron density profiles. In order to correlate the bilayer structure with the known lipid composition we have used step-function models to put the electron density profiles on an absolute scale and to define the quantitative distribution of molecular groups across the bilayer. This approach should provide a basis for interpreting the results from structural studies on the intact myelin membrane. Our myelin lipid profiles were typical of cholesterol-containing lipid bilayers with headgroup peaks at about ±23 Å from the central methyl group trough, and shoulders at about ±14 Å corresponding to the cholesterol nucleus. The electron density profiles of bilayers formed from peripheral nervous system and central nervous system myelin lipids were indistinguishable; however, we did find a small difference in thickness between mouse and bovine bilayers. We also observed clear and consistent differences between the bilayer profiles for the lipids extracted from mature and immature myelin. For both mature mouse and bovine lipid bilayers there was an increase in electron density at about ±14 Å from the bilayer center and a reduction in density at the headgroup peaks. These changes can be accounted for by an increase in membrane cholesterol content during maturation. We confirmed this by adding cholesterol to the immature lipids, forming multilayers and recording the X-ray diffraction patterns. The changes in the electron density profiles when cholesterol was added to the lipids closely paralleled the changes that we had observed during maturation.