title: Myelin organization in the nodal, paranodal, and juxtaparanodal regions revealed by scanning x-ray microdiffraction.
abstract: X-ray diffraction has provided extensive information about the arrangement of lipids and proteins in multilamellar myelin. This information has been limited to the abundant inter-nodal regions of the sheath because these regions dominate the scattering when x-ray beams of 100 µm diameter or more are used. Here, we used a 1 µm beam, raster-scanned across a single nerve fiber, to obtain detailed information about the molecular architecture in the nodal, paranodal, and juxtaparanodal regions. Orientation of the lamellar membrane stacks and membrane periodicity varied spatially. In the juxtaparanode-internode, 198-202 Å-period membrane arrays oriented normal to the nerve fiber axis predominated, whereas in the paranode-node, 205-208 Å-period arrays oriented along the fiber direction predominated. In parts of the sheath distal to the node, multiple sets of lamellar reflections were observed at angles to one another, suggesting that the myelin multilayers are deformed at the Schmidt-Lanterman incisures. The calculated electron density of myelin in the different regions exhibited membrane bilayer profiles with varied electron densities at the polar head groups, likely due to different amounts of major myelin proteins (P0 glycoprotein and myelin basic protein). Scattering from the center of the nerve fibers, where the x-rays are incident en face (perpendicular) to the membrane planes, provided information about the lateral distribution of protein. By underscoring the heterogeneity of membrane packing, microdiffraction analysis suggests a powerful new strategy for understanding the underlying molecular foundation of a broad spectrum of myelinopathies dependent on local specializations of myelin structure in both the PNS and CNS.
authors.affiliation: Department of Electrical and Computer Engineering, Northeastern University, Boston, Massachusetts, United States of America.
authors.forename: Hideyo
authors.initials: H
authors.lastname: Inouye
authors.affiliation: Department of Electrical and Computer Engineering, Northeastern University, Boston, Massachusetts, United States of America.
authors.forename: Jiliang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Electrical and Computer Engineering, Northeastern University, Boston, Massachusetts, United States of America; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, United States of America.
authors.forename: Lee
authors.initials: L
authors.lastname: Makowski
authors.affiliation: Division of Cell Biology & Genetics, Università Vita-Salute San Raffaele, Milano, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Palmisano
authors.affiliation: European Synchrotron Research Facility, Grenoble, France.
authors.forename: Manfred
authors.initials: M
authors.lastname: Burghammer
authors.affiliation: European Synchrotron Research Facility, Grenoble, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Riekel
authors.affiliation: Biology Department, Boston College, Chestnut Hill, Massachusetts, United States of America.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Kirschner
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D004676:Myelin Basic Protein / Q000737:chemistry* / Q000378:metabolism; D018993:Myelin P0 Protein / Q000737:chemistry* / Q000378:metabolism; D009186:Myelin Sheath / Q000737:chemistry* / Q000378:metabolism; D014961:X-Ray Diffraction
chemical_list: D004676:Myelin Basic Protein; D018993:Myelin P0 Protein