The Emergence of Electron Tomography as an Important Tool for Investigating Cellular UltrastructureBruce F. McEwena,b and Michael Markoaa Resource for Visualization of Biological Complexity, Division of Molecular Medicine, Wadsworth Center, New York State Department of Health, Albany, New York b Department of Biomedical Sciences, Graduate School of Public Health, State University of New York, Albany, New York Correspondence to: Bruce F. McEwen, Wadsworth Center, New York State Dept. of Health, PO Box 509, Albany, NY 12201-0509. E-mail: bruce.mcewen@wadsworth.org Electron tomography has emerged as the leading method for the study of three-dimensional (3D) ultrastructure in the 520-nm resolution range. It is ideally suited for studying cell organelles, subcellular assemblies and, in some cases, whole cells. Tomography occupies a place in 3D biological electron microscopy between the work now being done at near-atomic resolution on isolated macromolecules or 2D protein arrays and traditional serial-section reconstructions of whole cells and tissue specimens. Tomography complements serial-section reconstruction by providing higher resolution in the depth dimension, whereas serial-section reconstruction is better able to trace continuity over long distances throughout the depth of a cell. The two techniques can be combined with good results for favorable specimens. Tomography also complements 3D macromolecular studies by offering sufficient resolution to locate the macromolecular complexes in their cellular context. The technology has matured to the point at which application of electron tomography to specimens in plastic sections is routine, and new developments to overcome limitations due to beam exposure and specimen geometry promise to further improve its capabilities. In this review we give a brief description of the methodology and a summary of the new insights gained in a few representative applications. (J Histochem Cytochem 49:553563, 2001) Key Words: electron tomography, transmission electron, microscopy, three-dimensional, reconstruction, plastic embedding, cellular ultrastructure
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