The objective of the proposed research is to locate the various myelin proteins within the myelin membrane. These include the major myelin glycoprotein (Po) and the two myelin basic proteins (P1 and P2) in the peripheral nervous system (PNS) and the Folch-Lees proteolipid protein (PLP) and the basic myelin protein (A1) in the central nervous system (CNS). The results will define the normal structure of the nerve myelin sheath more precisely than is possible using electron microscopy or biochemical labelling alone. In turn, the results may help to detect structural changes in pathological states of the sheath. Electron-density profiles of the membranes in both PNS and CNS myelins will be obtained by analyzing the low-angle X-ray diffraction patterns. Myelins from various animals will be studied in order to take advantage of natural variations in the proportions of the various proteins. The electron-density profiles will be interpreted in terms of these variations and of the available biochemical and electron microscopical data. Lipids extracted from isolated myelin will be studied in order to understand their contribution to the myelin profile. As a further aid to the interpretation, artificial bilayer membranes consisting of myelin lipids and those myelin proteins which can be isolated also will be studied. Multilayer specimens consisting of membranes with known asymmetry will be made by picking up monolayers from the surface of a Langmuir trough. Alternative methods of making artificial membranes will be tried such as adding a protein to a suspension of single-walled lipid vesicles or by suspending lipids and a protein in a detergent micelles, mixing the two, and then dialyzing the detergent away. Where possible, the work will be done in collaboration with laboratories where the myelin proteins are being studied biochemically.