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Electron tomography of cells

Published online by Cambridge University Press:  15 November 2011

Lu Gan  and
Grant J. Jensen
Lu Gan
Affiliation:
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
Grant J. Jensen*
Affiliation:
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA
*
*Author for correspondence: G. J. Jensen. Tel.: (626) 395 – 8827; Fax: (626) 395 – 5730; Email: jensen@caltech.edu
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Abstract

The electron microscope has contributed deep insights into biological structure since its invention nearly 80 years ago. Advances in instrumentation and methodology in recent decades have now enabled electron tomography to become the highest resolution three-dimensional (3D) imaging technique available for unique objects such as cells. Cells can be imaged either plastic-embedded or frozen-hydrated. Then the series of projection images are aligned and back-projected to generate a 3D reconstruction or ‘tomogram’. Here, we review how electron tomography has begun to reveal the molecular organization of cells and how the existing and upcoming technologies promise even greater insights into structural cell biology.

Type
Review Article
Information
Quarterly Reviews of Biophysics , Volume 45 , Issue 1 , February 2012 , pp. 27 - 56
Copyright
Copyright © Cambridge University Press 2011

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References

7. References

Adrian, M., Dubochet, J., Lepault, J. & Mcdowall, A. W. (1984). Cryo-electron microscopy of viruses. Nature 308, 32–36.CrossRefGoogle ScholarPubMed
Al-Amoudi, A., Chang, J. J., Leforestier, A., Mcdowall, A., Salamin, L. M., Norlen, L. P., Richter, K., Blanc, N. S., Studer, D. & Dubochet, J. (2004). Cryo-electron microscopy of vitreous sections. EMBO Journal 23, 3583–3588.CrossRefGoogle ScholarPubMed
Al-Amoudi, A., Diez, D. C., Betts, M. J. & Frangakis, A. S. (2007). The molecular architecture of cadherins in native epidermal desmosomes. Nature 450, 832–837.CrossRefGoogle ScholarPubMed
Alon, U., Surette, M. G., Barkai, N. & Leibler, S. (1999). Robustness in bacterial chemotaxis. Nature 397, 168–171.CrossRefGoogle ScholarPubMed
Amat, F., Moussavi, F., Comolli, L. R., Elidan, G., Downing, K. H. & Horowitz, M. (2008). Markov random field based automatic image alignment for electron tomography. Journal of Structural Biology 161, 260–275.CrossRefGoogle ScholarPubMed
Beck, M., Forster, F., Ecke, M., Plitzko, J. M., Melchior, F., Gerisch, G., Baumeister, W. & Medalia, O. (2004). Nuclear pore complex structure and dynamics revealed by cryoelectron tomography. Science 306, 1387–1390.CrossRefGoogle ScholarPubMed
Beck, M., Lucic, V., Forster, F., Baumeister, W. & Medalia, O. (2007). Snapshots of nuclear pore complexes in action captured by cryo-electron tomography. Nature 449, 611–615.CrossRefGoogle ScholarPubMed
Beck, M., Malmstrom, J. A., Lange, V., Schmidt, A., Deutsch, E. W. & Aebersold, R. (2009). Visual proteomics of the human pathogen Leptospira interrogans. Nature Methods 6, 817–823.CrossRefGoogle ScholarPubMed
Belmont, A. S., Sedat, J. W. & Agard, D. A. (1987). A three-dimensional approach to mitotic chromosome structure: evidence for a complex hierarchical organization. Journal of Cell Biology 105, 77–92.CrossRefGoogle ScholarPubMed
Benjamin, J., Ganser-Pornillos, B. K., Tivol, W. F., Sundquist, W. I. & Jensen, G. J. (2005). Three-dimensional structure of HIV-1 virus-like particles by electron cryotomography. Journal of Molecular Biology 346, 577–588.CrossRefGoogle ScholarPubMed
Bennett, P. M. (1974). Decrease in section thickness on exposure to the electron beam; the use of tilted sections in estimating the amount of shrinkage. Journal of Cell Science 15(3), 693–701.CrossRefGoogle Scholar
Boggon, T. J., Murray, J., Chappuis-Flament, S., Wong, E., Gumbiner, B. M. & Shapiro, L. (2002). C-cadherin ectodomain structure and implications for cell adhesion mechanisms. Science 296, 1308–1313.CrossRefGoogle ScholarPubMed
Bottcher, B., Wynne, S. A. & Crowther, R. A. (1997). Determination of the fold of the core protein of hepatitis B virus by electron cryomicroscopy. Nature 386, 88–91.CrossRefGoogle ScholarPubMed
Bouchet-Marquis, C., Zuber, B., Glynn, A. M., Eltsov, M., Grabenbauer, M., Goldie, K. N., Thomas, D., Frangakis, A. S., Dubochet, J. & Chretien, D. (2007). Visualization of cell microtubules in their native state. Biology of the Cell 99, 45–53.CrossRefGoogle ScholarPubMed
Brandt, F., Carlson, L. A., Hartl, F. U., Baumeister, W. & Grunewald, K. (2010). The three-dimensional organization of polyribosomes in intact human cells. Molecular Cell 39, 560–569.CrossRefGoogle ScholarPubMed
Briegel, A., Dias, D. P., Li, Z., Jensen, R. B., Frangakis, A. S. & Jensen, G. J. (2006). Multiple large filament bundles observed in Caulobacter crescentus by electron cryotomography. Molecular Microbiology 62, 5–14.CrossRefGoogle ScholarPubMed
Briegel, A., Ding, H. J., Li, Z., Werner, J., Gitai, Z., Dias, D. P., Jensen, R. B. & Jensen, G. J. (2008). Location and architecture of the Caulobacter crescentus chemoreceptor array. Molecular Microbiology 69, 30–41.CrossRefGoogle ScholarPubMed
Briegel, A., Ortega, D. R., Tocheva, E. I., Wuichet, K., Li, Z., Chen, S., Muller, A., Iancu, C. V., Murphy, G. E., Dobro, M. J., Zhulin, I. B. & Jensen, G. J. (2009). Universal architecture of bacterial chemoreceptor arrays. Proceedings of the National Academy of Sciences of the United States of America 106(40), 17181–17186.CrossRefGoogle ScholarPubMed
Briggs, J. A., Grunewald, K., Glass, B., Forster, F., Krausslich, H. G. & Fuller, S. D. (2006). The mechanism of HIV-1 core assembly: insights from three-dimensional reconstructions of authentic virions. Structure 14, 15–20.CrossRefGoogle ScholarPubMed
Brumfield, S. K., Ortmann, A. C., Ruigrok, V., Suci, P., Douglas, T. & Young, M. J. (2009). Particle assembly and ultrastructural features associated with replication of the lytic archaeal virus sulfolobus turreted icosahedral virus. Journal of Virology 83, 5964–5970.CrossRefGoogle ScholarPubMed
Cambie, R., Downing, K. H., Typke, D., Glaeser, R. M. & Jin, J. (2007). Design of a microfabricated, two-electrode phase-contrast element suitable for electron microscopy. Ultramicroscopy 107(4–5), 329–339.CrossRefGoogle ScholarPubMed
Chang, J. T., Schmid, M. F., Haase-Pettingell, C., Weigele, P. R., King, J. A. & Chiu, W. (2010). Visualizing the structural changes of bacteriophage Epsilon15 and its Salmonella host during infection. Journal of Molecular Biology 402, 731–740.CrossRefGoogle ScholarPubMed
Chen, S., Beeby, M., Murphy, G. E., Leadbetter, J. R., Hendrixson, D. R., Briegel, A., Li, Z., Shi, J., Tocheva, E. I., Muller, A., Dobro, M. J. & Jensen, G. J. (2011). Structural diversity of bacterial flagellar motors. EMBO Journal 30, 2972–2981.CrossRefGoogle ScholarPubMed
Chen, S., Mcdowall, A., Dobro, M. J., Briegel, A., Ladinsky, M., Shi, J., Tocheva, E. I., Beeby, M., Pilhofer, M., Ding, H. J., Li, Z., Gan, L., Morris, D. M. & Jensen, G. J. (2010). Electron cryotomography of bacterial cells. Journal of Visualized Experiments (39), e1943.CrossRefGoogle ScholarPubMed
Chiu, S. W., Chen, S. Y. & Wong, H. C. (2008). Dynamic localization of MreB in Vibrio parahaemolyticus and in the ectopic host bacterium Escherichia coli. Applied and Environmental Microbiology 74, 6739–6745.CrossRefGoogle ScholarPubMed
Chretien, D., Fuller, S. D. & Karsenti, E. (1995). Structure of growing microtubule ends: two-dimensional sheets close into tubes at variable rates. Journal of Cell Biology 129, 1311–1328.Google Scholar
Clermont, Y., Rambourg, A. & Hermo, L. (1995). Trans-Golgi network (TGN) of different cell types: three-dimensional structural characteristics and variability. Anatomical Record 242, 289–301.CrossRefGoogle ScholarPubMed
Conway, J. F., Cheng, N., Zlotnick, A., Wingfield, P. T., Stahl, S. J. & Steven, A. C. (1997). Visualization of a 4-helix bundle in the hepatitis B virus capsid by cryo-electron microscopy. Nature 386, 91–94.CrossRefGoogle ScholarPubMed
Crowther, R. A., Derosier, D. J. & Klug, A. (1970). The reconstruction of a three-dimensional structure from projections and its application to electron microscopy. Proceedings of the Royal Society of London. Series A, Mathematical and Physical Sciences 317, 319–340.Google Scholar
Danev, R., Glaeser, R. M. & Nagayama, K. (2009). Practical factors affecting the performance of a thin-film phase plate for transmission electron microscopy. Ultramicroscopy 109, 312–325.CrossRefGoogle ScholarPubMed
Danev, R. & Nagayama, K. (2008). Single particle analysis based on Zernike phase contrast transmission electron microscopy. Journal of Structural Biology 161, 211–218.CrossRefGoogle ScholarPubMed
Deptuch, G., Besson, A., Rehak, P., Szelezniak, M., Wall, J., Winter, M. & Zhu, Y. (2007). Direct electron imaging in electron microscopy with monolithic active pixel sensors. Ultramicroscopy 107, 674–684.CrossRefGoogle ScholarPubMed
Diestra, E., Fontana, J., Guichard, P., Marco, S. & Risco, C. (2009). Visualization of proteins in intact cells with a clonable tag for electron microscopy. Journal of Structural Biology 165, 157–168.CrossRefGoogle ScholarPubMed
Ding, R., Mcdonald, K. L. & Mcintosh, J. R. (1993). Three-dimensional reconstruction and analysis of mitotic spindles from the yeast, Schizosaccharomyces pombe. Journal of Cell Biology 120, 141–151.CrossRefGoogle ScholarPubMed
Dominguez-Escobar, J., Chastanet, A., Crevenna, A. H., Fromion, V., Wedlich-Soldner, R. & Carballido-Lopez, R. (2011). Processive movement of MreB-associated cell wall biosynthetic complexes in bacteria. Science 333, 225–228.CrossRefGoogle ScholarPubMed
Dubochet, J., Adrian, M., Chang, J. J., Homo, J. C., Lepault, J., Mcdowall, A. W. & Schultz, P. (1988). Cryo-electron microscopy of vitrified specimens. Quarterly Review of Biophysics 21, 129–228.CrossRefGoogle ScholarPubMed
Dubochet, J., Mcdowall, A. W., Menge, B., Schmid, E. N. & Lickfeld, K. G. (1983). Electron microscopy of frozen-hydrated bacteria. Journal of Bacteriology 155, 381–390.CrossRefGoogle ScholarPubMed
Dubochet, J., Zuber, B., Eltsov, M., Bouchet-Marquis, C., Al-Amoudi, A. & Livolant, F. (2007). How to ‘read’ a vitreous section. Methods in Cell Biology 79, 385–406.CrossRefGoogle Scholar
Erickson, H. P. (1997). FtsZ, a tubulin homologue in prokaryote cell division. Trends in Cell Biology 7, 362–367.CrossRefGoogle ScholarPubMed
Fan, G. Y., Mercurio, P. J., Young, S. J. & Ellisman, M. H. (1993). Telemicroscopy. Ultramicroscopy 52, 499–503.CrossRefGoogle ScholarPubMed
Fernandez, J. J., Li, S. & Crowther, R. A. (2006). CTF determination and correction in electron cryotomography. Ultramicroscopy 106, 587–596.Google Scholar
Figge, R. M., Divakaruni, A. V. & Gober, J. W. (2004). MreB, the cell shape-determining bacterial actin homologue, co-ordinates cell wall morphogenesis in Caulobacter crescentus. Molecular Microbiology 51, 1321–1332.CrossRefGoogle ScholarPubMed
Forster, F. (2005). Quantitative Analysis of Macromolecules in Cryoelectron Tomograms using Correlation Methods. Technical University of Munich, Munich, Germany.Google Scholar
Frangakis, A. S. & Hegerl, R. (2001). Noise reduction in electron tomographic reconstructions using nonlinear anisotropic diffusion. Journal of Structural Biology 135, 239–250.CrossRefGoogle ScholarPubMed
Frank, J. (2006). Electron Tomography: Methods for Three-Dimensional Visualization of Structures in the Cell, 2nd edn. London, New York: Springer.Google Scholar
Frederik, P. M. & Hubert, D. H. (2005). Cryoelectron microscopy of liposomes. Methods in Enzymology 391, 431–448.CrossRefGoogle ScholarPubMed
Fu, C. Y., Wang, K., Gan, L., Lanman, J., Khayat, R., Young, M. J., Jensen, G. J., Doerschuk, P. C. & Johnson, J. E. (2010). In vivo assembly of an archaeal virus studied with whole-cell electron cryotomography. Structure 18, 1579–1586.Google Scholar
Gaietta, G., Deerinck, T. J., Adams, S. R., Bouwer, J., Tour, O., Laird, D. W., Sosinsky, G. E., Tsien, R. Y. & Ellisman, M. H. (2002). Multicolor and electron microscopic imaging of connexin trafficking. Science 296, 503–507.CrossRefGoogle ScholarPubMed
Gan, L., Ladinsky, M. S. & Jensen, G. J. (2011). Organization of the smallest eukaryotic spindle. Current Biology 21, 1578–1583.CrossRefGoogle ScholarPubMed
Garner, E. C., Bernard, R., Wang, W., Zhuang, X., Rudner, D. Z. & Mitchison, T. (2011). Coupled, circumferential motions of the cell wall synthesis machinery and MreB filaments in B. subtilis. Science 333, 222–225.Google Scholar
Gilbert, P. (1972). Iterative methods for the three-dimensional reconstruction of an object from projections. Journal of Theoretical Biology 36, 105–117.CrossRefGoogle ScholarPubMed
Gilkey, J. C. & Staehelin, L. A. (1986). Advances in ultrarapid freezing for the preservation of cellular ultrastructure. Journal of Electron Microscopy Technique 3, 177–210.CrossRefGoogle Scholar
Gitai, Z. (2005). The new bacterial cell biology: moving parts and subcellular architecture. Cell 120, 577–586.Google Scholar
Goodsell, D. S. (2005). Visual methods from atoms to cells. Structure 13, 347–354.CrossRefGoogle ScholarPubMed
Grunewald, K., Desai, P., Winkler, D. C., Heymann, J. B., Belnap, D. M., Baumeister, W. & Steven, A. C. (2003). Three-dimensional structure of herpes simplex virus from cryo-electron tomography. Science 302, 1396–1398.CrossRefGoogle ScholarPubMed
Gruska, M., Medalia, O., Baumeister, W. & Leis, A. (2008). Electron tomography of vitreous sections from cultured mammalian cells. Journal of Structural Biology 161, 384–392.CrossRefGoogle ScholarPubMed
Harris, A., Cardone, G., Winkler, D. C., Heymann, J. B., Brecher, M., White, J. M. & Steven, A. C. (2006). Influenza virus pleiomorphy characterized by cryoelectron tomography. Proceedings of the National Academy of Sciences of the United States of America 103, 19123–19127.CrossRefGoogle ScholarPubMed
Hayles, M. F., Matthijs De Winter, D. A., Schneijdenberg, C. T., Meeldijk, J. D., Luecken, U., Persoon, H., De Water, J., De Jong, F., Humbel, B. M. & Verkleij, A. J. (2010). The making of frozen-hydrated, vitreous lamellas from cells for cryo-electron microscopy. Journal of Structural Biology 172, 180–190.CrossRefGoogle ScholarPubMed
He, W., Cowin, P. & Stokes, D. L. (2003). Untangling desmosomal knots with electron tomography. Science 302, 109–113.Google Scholar
He, W., Kivork, C., Machinani, S., Morphew, M. K., Gail, A. M., Tesar, D. B., Tiangco, N. E., Mcintosh, J. R. & Bjorkman, P. J. (2007). A freeze substitution fixation-based gold enlarging technique for EM studies of endocytosed nanogold-labeled molecules. Journal of Structural Biology 160, 103–113.CrossRefGoogle ScholarPubMed
He, W., Ladinsky, M. S., Huey-Tubman, K. E., Jensen, G. J., Mcintosh, J. R. & Bjorkman, P. J. (2008). FcRn-mediated antibody transport across epithelial cells revealed by electron tomography. Nature 455, 542–546.Google Scholar
Henderson, G. P., Gan, L. & Jensen, G. J. (2007). 3-D ultrastructure of O. tauri: electron cryotomography of an entire eukaryotic cell. PloS ONE 2, e749.CrossRefGoogle Scholar
Henderson, R., Baldwin, J. M., Ceska, T. A., Zemlin, F., Beckmann, E. & Downing, K. H. (1990). Model for the structure of bacteriorhodopsin based on high-resolution electron cryo-microscopy. Journal of Molecular Biology 213, 899–929.CrossRefGoogle ScholarPubMed
Herman, G. T., Lent, A. & Rowland, S. W. (1973). ART: mathematics and applications. A report on the mathematical foundations and on the applicability to real data of the algebraic reconstruction techniques. Journal of Theoretical Biology 42, 1–32.Google Scholar
Heymann, J. B., Cardone, G., Winkler, D. C. & Steven, A. C. (2008). Computational resources for cryo-electron tomography in Bsoft. Journal of Structural Biology 161, 232–242.CrossRefGoogle ScholarPubMed
Hoppe, W., Gassmann, J., Hunsmann, N., Schramm, H. J. & Sturm, M. (1974). Three-dimensional reconstruction of individual negatively stained yeast fatty-acid synthetase molecules from tilt series in the electron microscope. Hoppe-Seylers Zeitschrift für Physiologische Chemie 355, 1483–1487.Google ScholarPubMed
Hsieh, C. E., Marko, M., Frank, J. & Mannella, C. A. (2002). Electron tomographic analysis of frozen-hydrated tissue sections. Journal of Structural Biology 138, 63–73.CrossRefGoogle ScholarPubMed
Iancu, C. V., Morris, D. M., Dou, Z., Heinhorst, S., Cannon, G. C. & Jensen, G. J. (2010). Organization, structure, and assembly of alpha-carboxysomes determined by electron cryotomography of intact cells. Journal of Molecular Biology 396, 105–117.Google Scholar
Iancu, C. V., Tivol, W. F., Schooler, J. B., Dias, D. P., Henderson, G. P., Murphy, G. E., Wright, E. R., Li, Z., Yu, Z., Briegel, A., Gan, L., He, Y. & Jensen, G. J. (2006a). Electron cryotomography sample preparation using the Vitrobot. Nature Protocols 1, 2813–2819.CrossRefGoogle ScholarPubMed
Iancu, C. V., Wright, E. R., Benjamin, J., Tivol, W. F., Dias, D. P., Murphy, G. E., Morrison, R. C., Heymann, J. B. & Jensen, G. J. (2005). A ‘flip-flop’ rotation stage for routine dual-axis electron cryotomography. Journal of Structural Biology 151, 288–297.CrossRefGoogle ScholarPubMed
Iancu, C. V., Wright, E. R., Heymann, J. B. & Jensen, G. J. (2006b). A comparison of liquid nitrogen and liquid helium as cryogens for electron cryotomography. Journal of Structural Biology 153, 231–240.Google Scholar
Ingerson-Mahar, M., Briegel, A., Werner, J. N., Jensen, G. J. & Gitai, Z. (2010). The metabolic enzyme CTP synthase forms cytoskeletal filaments. Nature Cell Biology 12, 739–746.CrossRefGoogle ScholarPubMed
Jones, L. J., Carballido-Lopez, R. & Errington, J. (2001). Control of cell shape in bacteria: helical, actin-like filaments in Bacillus subtilis. Cell 104, 913–922.CrossRefGoogle ScholarPubMed
Khayat, R., Tang, L., Larson, E. T., Lawrence, C. M., Young, M. & Johnson, J. E. (2005). Structure of an archaeal virus capsid protein reveals a common ancestry to eukaryotic and bacterial viruses. Proceedings of the National Academy of Sciences of the United States of America 102, 18944–18949.CrossRefGoogle ScholarPubMed
Khursigara, C. M., Wu, X. & Subramaniam, S. (2008a). Chemoreceptors in Caulobacter crescentus: trimers of receptor dimers in a partially ordered hexagonally packed array. Journal of Bacteriology 190, 6805–6810.CrossRefGoogle Scholar
Khursigara, C. M., Wu, X., Zhang, P., Lefman, J. & Subramaniam, S. (2008b). Role of HAMP domains in chemotaxis signaling by bacterial chemoreceptors. Proceedings of the National Academy of Sciences, USA 105, 16555–16560.CrossRefGoogle ScholarPubMed
Komeili, A., Li, Z., Newman, D. K. & Jensen, G. J. (2006). Magnetosomes are cell membrane invaginations organized by the actin-like protein MamK. Science 311, 242–245.CrossRefGoogle ScholarPubMed
Koster, A. J., Grimm, R., Typke, D., Hegerl, R., Stoschek, A., Walz, J. & Baumeister, W. (1997). Perspectives of molecular and cellular electron tomography. Journal of Structural Biology 120, 276–308.CrossRefGoogle ScholarPubMed
Kremer, J. R., Mastronarde, D. N. & Mcintosh, J. R. (1996). Computer visualization of three-dimensional image data using IMOD. Journal of Structural Biology 116, 71–76.CrossRefGoogle ScholarPubMed
Kudryashev, M., Cyrklaff, M., Wallich, R., Baumeister, W. & Frischknecht, F. (2010). Distinct in situ structures of the Borrelia flagellar motor. Journal of Structural Biology 169, 54–61.CrossRefGoogle ScholarPubMed
Kurner, J., Frangakis, A. S. & Baumeister, W. (2005). Cryo-electron tomography reveals the cytoskeletal structure of Spiroplasma melliferum. Science 307, 436–438.CrossRefGoogle ScholarPubMed
Ladinsky, M. S. & Howell, K. E. (2007). Electron tomography of immunolabeled cryosections. Methods in Cell Biology 79, 543–558.CrossRefGoogle ScholarPubMed
Ladinsky, M. S., Mastronarde, D. N., Mcintosh, J. R., Howell, K. E. & Staehelin, L. A. (1999). Golgi structure in three dimensions: functional insights from the normal rat kidney cell. Journal of Cell Biology 144, 1135–1149.CrossRefGoogle ScholarPubMed
Ladinsky, M. S., Pierson, J. M. & Mcintosh, J. R. (2006). Vitreous cryo-sectioning of cells facilitated by a micromanipulator. Journal of Microscopy 224, 129–134.CrossRefGoogle ScholarPubMed
Lawrence, A., Bouwer, J. C., Perkins, G. & Ellisman, M. H. (2006). Transform-based backprojection for volume reconstruction of large format electron microscope tilt series. Journal of Structural Biology 154, 144–167.CrossRefGoogle ScholarPubMed
Lee, E., Fahimian, B. P., Iancu, C. V., Suloway, C., Murphy, G. E., Wright, E. R., Castano-Diez, D., Jensen, G. J. & Miao, J. (2008). Radiation dose reduction and image enhancement in biological imaging through equally-sloped tomography. Journal of Structural Biology 164, 221–227.CrossRefGoogle ScholarPubMed
Lenzi, D., Crum, J., Ellisman, M. H. & Roberts, W. M. (2002). Depolarization redistributes synaptic membrane and creates a gradient of vesicles on the synaptic body at a ribbon synapse. Neuron 36, 649–659.Google Scholar
Lenzi, D., Runyeon, J. W., Crum, J., Ellisman, M. H. & Roberts, W. M. (1999). Synaptic vesicle populations in saccular hair cells reconstructed by electron tomography. Journal of Neuroscience 19, 119–132.CrossRefGoogle ScholarPubMed
Li, Z., Trimble, M. J., Brun, Y. V. & Jensen, G. J. (2007). The structure of FtsZ filaments in vivo suggests a force-generating role in cell division. EMBO Journal 26(22), 4694–4708.CrossRefGoogle ScholarPubMed
Liu, H., Jin, L., Koh, S. B., Atanasov, I., Schein, S., Wu, L. & Zhou, Z. H. (2010). Atomic structure of human adenovirus by cryo-EM reveals interactions among protein networks. Science 329, 1038–1043.Google Scholar
Liu, J., Lin, T., Botkin, D. J., Mccrum, E., Winkler, H. & Norris, S. J. (2009). Intact flagellar motor of Borrelia burgdorferi revealed by cryo-electron tomography: evidence for stator ring curvature and rotor/C-ring assembly flexion. Journal of Bacteriology 191, 5026–5036.CrossRefGoogle ScholarPubMed
Lucic, V., Forster, F. & Baumeister, W. (2005). Structural studies by electron tomography: from cells to molecules. Annual Review of Biochemistry 74, 833–865.Google Scholar
Majorovits, E., Barton, B., Schultheiss, K., Perez-Willard, F., Gerthsen, D. & Schroder, R. R. (2007). Optimizing phase contrast in transmission electron microscopy with an electrostatic (Boersch) phase plate. Ultramicroscopy 107, 213–226.CrossRefGoogle ScholarPubMed
Mandelkow, E. M., Mandelkow, E. & Milligan, R. A. (1991). Microtubule dynamics and microtubule caps: a time-resolved cryo-electron microscopy study. Journal of Cell Biology 114, 977–991.Google Scholar
Marko, M., Hsieh, C., Schalek, R., Frank, J. & Mannella, C. (2007). Focused-ion-beam thinning of frozen-hydrated biological specimens for cryo-electron microscopy. Nature Methods 4, 215–217.Google Scholar
Marsh, B. J. (2007). Reconstructing mammalian membrane architecture by large area cellular tomography. Methods in Cell Biology 79, 193–220.Google Scholar
Marsh, B. J., Mastronarde, D. N., Buttle, K. F., Howell, K. E. & Mcintosh, J. R. (2001). Organellar relationships in the Golgi region of the pancreatic beta cell line, HIT-T15, visualized by high resolution electron tomography. Proceedings of the National Academy of Sciences of the United States of America 98, 2399–2406.CrossRefGoogle ScholarPubMed
Marsh, B. J., Volkmann, N., Mcintosh, J. R. & Howell, K. E. (2004). Direct continuities between cisternae at different levels of the Golgi complex in glucose-stimulated mouse islet beta cells. Proceedings of the National Academy of Sciences of the United States of America 101, 5565–5570.CrossRefGoogle ScholarPubMed
Masich, S., Ostberg, T., Norlen, L., Shupliakov, O. & Daneholt, B. (2006). A procedure to deposit fiducial markers on vitreous cryo-sections for cellular tomography. Journal of Structural Biology 156(3), 461–468.Google Scholar
Mastronarde, D. N. (1997). Dual-axis tomography: an approach with alignment methods that preserve resolution. Journal of Structural Biology 120, 343–352.CrossRefGoogle ScholarPubMed
Mastronarde, D. N. (2005). Automated electron microscope tomography using robust prediction of specimen movements. Journal of Structural Biology 152, 36–51.Google Scholar
Mastronarde, D. N., Ladinsky, M. S. & Mcintosh, J. R. (2000). Super-thin serial sectioning for high resolution 3-D reconstruction of cellular structures. Microscopy and Microanalysis, 3, 221–222.CrossRefGoogle Scholar
Mcdonald, K. L. (2009). A review of high-pressure freezing preparation techniques for correlative light and electron microscopy of the same cells and tissues. Journal of microscopy 235, 273–281.CrossRefGoogle ScholarPubMed
Mcdonald, K. L. & Auer, M. (2006). High-pressure freezing, cellular tomography, and structural cell biology. Biotechniques 41, 137–143.Google Scholar
Mcewen, B. F., Downing, K. H. & Glaeser, R. M. (1995). The relevance of dose-fractionation in tomography of radiation-sensitive specimens. Ultramicroscopy 60, 357–373.CrossRefGoogle ScholarPubMed
Mcewen, B. F., Radermacher, M., Rieder, C. L. & Frank, J. (1986). Tomographic three-dimensional reconstruction of cilia ultrastructure from thick sections. Proceedings of the National Academy of Sciences of the United States of America 83, 9040–9044.CrossRefGoogle ScholarPubMed
Mcintosh, J. R., Grishchuk, E. L., Morphew, M. K., Efremov, A. K., Zhudenkov, K., Volkov, V. A., Cheeseman, I. M., Desai, A., Mastronarde, D. N. & Ataullakhanov, F. I. (2008). Fibrils connect microtubule tips with kinetochores: a mechanism to couple tubulin dynamics to chromosome motion. Cell 135, 322–333.CrossRefGoogle ScholarPubMed
Mcintosh, J. R., Roos, U. P., Neighbors, B. & Mcdonald, K. L. (1985). Architecture of the microtubule component of mitotic spindles from Dictyostelium discoideum. Journal of Cell Science 75, 93–129.Google Scholar
Mcmullan, G., Cattermole, D. M., Chen, S., Henderson, R., Llopart, X., Summerfield, C., Tlustos, L. & Faruqi, A. R. (2007). Electron imaging with Medipix2 hybrid pixel detector. Ultramicroscopy 107, 401–413.Google Scholar
Mcmullan, G., Clark, A. T., Turchetta, R. & Faruqi, A. R. (2009). Enhanced imaging in low dose electron microscopy using electron counting. Ultramicroscopy 109, 1411–1416.Google Scholar
Medalia, O., Weber, I., Frangakis, A. S., Nicastro, D., Gerisch, G. & Baumeister, W. (2002). Macromolecular architecture in eukaryotic cells visualized by cryoelectron tomography. Science 298, 1209–1213.Google Scholar
Mercogliano, C. P. & Derosier, D. J. (2007). Concatenated metallothionein as a clonable gold label for electron microscopy. Journal of Structural Biology 160, 70–82.CrossRefGoogle ScholarPubMed
Messaoudii, C., Boudier, T., Sanchez Sorzano, C. O. & Marco, S. (2007). TomoJ: tomography software for three-dimensional reconstruction in transmission electron microscopy. BMC Bioinformatics 8, 288.Google Scholar
Milazzo, A. C., Leblanc, P., Duttweiler, F., Jin, L., Bouwer, J. C., Peltier, S., Ellisman, M., Bieser, F., Matis, H. S., Wieman, H., Denes, P., Kleinfelder, S. & Xuong, N. H. (2005). Active pixel sensor array as a detector for electron microscopy. Ultramicroscopy 104, 152–159.Google Scholar
Milne, J. L. & Subramaniam, S. (2009). Cryo-electron tomography of bacteria: progress, challenges and future prospects. Nature Reviews Microbiology 7, 666–675.Google Scholar
Minton, A. P. (2006). How can biochemical reactions within cells differ from those in test tubes? Journal of Cell Science 119, 2863–2869.Google Scholar
Moor, H. (1987). Theory and Practice of High Pressure Freezing. Berlin: Springer-Verlag.Google Scholar
Moritz, M., Braunfeld, M. B., Guenebaut, V., Heuser, J. & Agard, D. A. (2000). Structure of the gamma-tubulin ring complex: a template for microtubule nucleation. Nature Cell Biology 2, 365–370.Google Scholar
Morphew, M., He, W., Bjorkman, P. J. & Mcintosh, J. R. (2008). Silver enhancement of Nanogold particles during freeze substitution for electron microscopy. Journal of Microscopy 230, 263–267.CrossRefGoogle ScholarPubMed
Murphy, G. E. & Jensen, G. J. (2005). Electron cryotomography of the E. coli pyruvate and 2-oxoglutarate dehydrogenase complexes. Structure 13, 1765–1773.Google Scholar
Murphy, G. E., Leadbetter, J. R. & Jensen, G. J. (2006). In situ structure of the complete Treponema primitia flagellar motor. Nature 442, 1062–1064.CrossRefGoogle ScholarPubMed
Murphy, G. E., Lowekamp, B. C., Zerfas, P. M., Chandler, R. J., Narasimha, R., Venditti, C. P. & Subramaniam, S. (2010). Ion-abrasion scanning electron microscopy reveals distorted liver mitochondrial morphology in murine methylmalonic acidemia. Journal of Structural Biology 171, 125–132.Google Scholar
Murphy, G. E., Matson, E. G., Leadbetter, J. R., Berg, H. C. & Jensen, G. J. (2008). Novel ultrastructures of Treponema primitia and their implications for motility. Molecular Microbiology 67, 1184–1195.Google Scholar
Nagayama, K. & Danev, R. (2009). Phase-plate electron microscopy: a novel imaging tool to reveal close-to-life nano-structures. Biophysical Reviews 1, 37–42.CrossRefGoogle ScholarPubMed
Nickell, S., Forster, F., Linaroudis, A., Net, W. D., Beck, F., Hegerl, R., Baumeister, W. & Plitzko, J. M. (2005). TOM software toolbox: acquisition and analysis for electron tomography. Journal of Structural Biology 149(3), 227–234.Google Scholar
Nickell, S., Kofler, C., Leis, A. P. & Baumeister, W. (2006). A visual approach to proteomics. Nature Reviews Molecular Cell Biology 7, 225–230.Google Scholar
Noske, A. B., Costin, A. J., Morgan, G. P. & Marsh, B. J. (2008). Expedited approaches to whole cell electron tomography and organelle mark-up in situ in high-pressure frozen pancreatic islets. Journal of Structural Biology 161, 298–313.CrossRefGoogle ScholarPubMed
O'toole, E. T., Mcdonald, K. L., Mantler, J., Mcintosh, J. R., Hyman, A. A. & Muller-Reichert, T. (2003). Morphologically distinct microtubule ends in the mitotic centrosome of Caenorhabditis elegans. Journal of Cell Biology 163, 451–456.CrossRefGoogle ScholarPubMed
O'toole, E. T., Winey, M. & Mcintosh, J. R. (1999). High-voltage electron tomography of spindle pole bodies and early mitotic spindles in the yeast Saccharomyces cerevisiae. Molecular Biology Cell 10, 2017–2031.Google Scholar
Olins, D. E., Olins, A. L., Levy, H. A., Durfee, R. C., Margle, S. M., Tinnel, E. P. & Dover, S. D. (1983). Electron microscope tomography: transcription in three dimensions. Science 220, 498–500.Google Scholar
Ortiz, J. O., Brandt, F., Matias, V. R., Sennels, L., Rappsilber, J., Scheres, S. H., Eibauer, M., Hartl, F. U. & Baumeister, W. (2010). Structure of hibernating ribosomes studied by cryoelectron tomography in vitro and in situ. Journal of Cell Biology 190, 613–621.CrossRefGoogle ScholarPubMed
Ortiz, J. O., Forster, F., Kurner, J., Linaroudis, A. A. & Baumeister, W. (2006). Mapping 70S ribosomes in intact cells by cryoelectron tomography and pattern recognition. Journal of Structural Biology 156, 334–341.CrossRefGoogle ScholarPubMed
Overby, A. K., Pettersson, R. F., Grunewald, K. & Huiskonen, J. T. (2008). Insights into bunyavirus architecture from electron cryotomography of Uukuniemi virus. Proceedings of the National Academy of Sciences of the United States of America 105, 2375–2379.CrossRefGoogle ScholarPubMed
Patla, I., Volberg, T., Elad, N., Hirschfeld-Warneken, V., Grashoff, C., Fassler, R., Spatz, J. P., Geiger, B. & Medalia, O. (2010). Dissecting the molecular architecture of integrin adhesion sites by cryo-electron tomography. Nature Cell Biology 12, 909–915.CrossRefGoogle ScholarPubMed
Penczek, P. A. (2010a). Fundamentals of three-dimensional reconstruction from projections. Methods in Enzymology 482, 1–33.Google Scholar
Penczek, P. A. (2010b). Image restoration in cryo-electron microscopy. Methods in Enzymology 482, 35–72.Google Scholar
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C. & Ferrin, T. E. (2004). UCSF Chimera – a visualization system for exploratory research and analysis. Journal of Computational Chemistry 25, 1605–1612.Google Scholar
Pierson, J., Fernandez, J. J., Bos, E., Amini, S., Gnaegi, H., Vos, M., Bel, B., Adolfsen, F., Carrascosa, J. L. & Peters, P. J. (2010). Improving the technique of vitreous cryo-sectioning for cryo-electron tomography: electrostatic charging for section attachment and implementation of an anti-contamination glove box. Journal of Structural Biology 169, 219–225.CrossRefGoogle ScholarPubMed
Pilhofer, M., Ladinsky, M. S., Mcdowall, A. W. & Jensen, G. J. (2010). Bacterial TEM: new insights from cryo-microscopy. Methods in Cell Biology 96, 21–45.Google Scholar
Ress, D., Harlow, M. L., Schwarz, M., Marshall, R. M. & Mcmahan, U. J. (1999). Automatic acquisition of fiducial markers and alignment of images in tilt series for electron tomography. Journal of Electron Microscopy (Tokyo) 48, 277–287.CrossRefGoogle ScholarPubMed
Rigort, A., Bauerlein, F. J., Leis, A., Gruska, M., Hoffmann, C., Laugks, T., Bohm, U., Eibauer, M., Gnaegi, H., Baumeister, W. & Plitzko, J. M. (2010). Micromachining tools and correlative approaches for cellular cryo-electron tomography. Journal of Structural Biology 172, 169–179.Google Scholar
Salje, J., Zuber, B. & Lowe, J. (2009). Electron cryomicroscopy of E. coli reveals filament bundles involved in plasmid DNA segregation. Science 323, 509–512.Google Scholar
Sandberg, K. & Brega, M. (2007). Segmentation of thin structures in electron micrographs using orientation fields. Journal of Structural Biology 157, 403–415.Google Scholar
Saxton, W. O., Baumeister, W. & Hahn, M. (1984). Three-dimensional reconstruction of imperfect two-dimensional crystals. Ultramicroscopy 13, 57–70.CrossRefGoogle ScholarPubMed
Scheffel, A., Gruska, M., Faivre, D., Linaroudis, A., Plitzko, J. M. & Schuler, D. (2006). An acidic protein aligns magnetosomes along a filamentous structure in magnetotactic bacteria. Nature 440, 110–114.CrossRefGoogle ScholarPubMed
Scheres, S. H., Melero, R., Valle, M. & Carazo, J. M. (2009). Averaging of electron subtomograms and random conical tilt reconstructions through likelihood optimization. Structure 17, 1563–1572.CrossRefGoogle ScholarPubMed
Schwartz, C. L., Sarbash, V. I., Ataullakhanov, F. I., Mcintosh, J. R. & Nicastro, D. (2007). Cryo-fluorescence microscopy facilitates correlations between light and cryo-electron microscopy and reduces the rate of photobleaching. Journal of Microscopy 227, 98–109.Google Scholar
Seybert, A., Herrmann, R. & Frangakis, A. S. (2006). Structural analysis of Mycoplasma pneumoniae by cryo-electron tomography. Journal of Structural Biology 156, 342–354.CrossRefGoogle ScholarPubMed
Shaikh, T. R., Gao, H., Baxter, W. T., Asturias, F. J., Boisset, N., Leith, A. & Frank, J. (2008). SPIDER image processing for single-particle reconstruction of biological macromolecules from electron micrographs. Nature Protocol 3, 1941–1974.Google Scholar
Shih, Y. L., Le, T. & Rothfield, L. (2003). Division site selection in Escherichia coli involves dynamic redistribution of Min proteins within coiled structures that extend between the two cell poles. Proceedings of the National Academy of Sciences, USA 100(13), 7865–7870.CrossRefGoogle ScholarPubMed
Sigworth, F. J. (1998). A maximum-likelihood approach to single-particle image refinement. Journal of Structural Biology 122, 328–339.Google Scholar
Skoglund, U., Andersson, K., Strandberg, B. & Daneholt, B. (1986). Three-dimensional structure of a specific pre-messenger RNP particle established by electron microscope tomography. Nature 319, 560–564.Google Scholar
Soto, G. E., Young, S. J., Martone, M. E., Deerinck, T. J., Lamont, S., Carragher, B. O., Hama, K. & Ellisman, M. H. (1994). Serial section electron tomography: a method for three-dimensional reconstruction of large structures. Neuroimage 1, 230–243.CrossRefGoogle ScholarPubMed
Sougrat, R., Bartesaghi, A., Lifson, J. D., Bennett, A. E., Bess, J. W., Zabransky, D. J. & Subramaniam, S. (2007). Electron tomography of the contact between T cells and SIV/HIV-1: implications for viral entry. PLoS Pathogen 3, e63.CrossRefGoogle ScholarPubMed
Srivastava, P., Demarre, G., Karpova, T. S., Mcnally, J. & Chattoraj, D. K. (2007). Changes in nucleoid morphology and origin localization upon inhibition or alteration of the actin homolog, MreB, of Vibrio cholerae. Journal of Bacteriology 189, 7450–7463.Google Scholar
Suloway, C., Shi, J., Cheng, A., Pulokas, J., Carragher, B., Potter, C. S., Zheng, S. Q., Agard, D. A. & Jensen, G. J. (2009). Fully automated, sequential tilt-series acquisition with Leginon. Journal of Structural Biology 167, 11–18.CrossRefGoogle ScholarPubMed
Swulius, M. T., Chen, S., Jane Ding, H., Li, Z., Briegel, A., Pilhofer, M., Tocheva, E. I., Lybarger, S. R., Johnson, T. L., Sandkvist, M. & Jensen, G. J. (2011). Long helical filaments are not seen encircling cells in electron cryotomograms of rod-shaped bacteria. Biochemical and Biophysical Research Communications 407, 650–655.Google Scholar
Tang, H., Braun, T. F. & Blair, D. F. (1996). Motility protein complexes in the bacterial flagellar motor. Journal of Molecular Biology 261, 209–221.CrossRefGoogle ScholarPubMed
Taylor, K. A. & Glaeser, R. M. (1974). Electron diffraction of frozen, hydrated protein crystals. Science 186, 1036–1037.Google Scholar
Thomas, D., Morgan, D. G. & Derosier, D. J. (2001). Structures of bacterial flagellar motors from two FliF–FliG gene fusion mutants. Journal of Bacteriology 183, 6404–6412.Google Scholar
Tocheva, E. I., Li, Z. & Jensen, G. J. (2010). Electron cryotomography. Cold Spring Harbor Perspectives in Biology 2, a003442.CrossRefGoogle ScholarPubMed
Tokuyasu, K. T. (1986). Application of cryoultramicrotomy to immunocytochemistry. Journal of Microscopy 143, 139–149.Google Scholar
Trucco, A., Polishchuk, R. S., Martella, O., Di Pentima, A., Fusella, A., Di Giandomenico, D., San Pietro, E., Beznoussenko, G. V., Polishchuk, E. V., Baldassarre, M., Buccione, R., Geerts, W. J., Koster, A. J., Burger, K. N., Mironov, A. A. & Luini, A. (2004). Secretory traffic triggers the formation of tubular continuities across Golgi sub-compartments. Nature Cell Biology 6, 1071–1081.Google Scholar
Urban, E., Jacob, S., Nemethova, M., Resch, G. P. & Small, J. V. (2010). Electron tomography reveals unbranched networks of actin filaments in lamellipodia. Nature Cell Biology 12, 429–435.Google Scholar
Van Der Heide, P., Xu, X. P., Marsh, B. J., Hanein, D. & Volkmann, N. (2007). Efficient automatic noise reduction of electron tomographic reconstructions based on iterative median filtering. Journal of Structural Biology 158, 196–204.Google Scholar
Vandenbeldt, K. J., Barnard, R. M., Hergert, P. J., Meng, X., Maiato, H. & Mcewen, B. F. (2006). Kinetochores use a novel mechanism for coordinating the dynamics of individual microtubules. Current Biology 16, 1217–1223.Google Scholar
Volkmann, N. (2002). A novel three-dimensional variant of the watershed transform for segmentation of electron density maps. Journal of Structural Biology 138, 123–129.CrossRefGoogle ScholarPubMed
Wang, Q., Mercogliano, C. P. & Lowe, J. (2011). A ferritin-based label for cellular electron cryotomography. Structure 19, 147–154.Google Scholar
Wei, D. Y. & Yin, C. C. (2010). An optimized locally adaptive non-local means denoising filter for cryo-electron microscopy data. Journal of Structural Biology 172, 211–218.Google Scholar
White, J. G., Southgate, E., Thomson, J. N. & Brenner, S. (1986). The structure of the nervous system of the nematode Caenorhabditis elegans. Philosophical Transactions of the Royal Society of London. B, Biological Sciences 314, 1–340.Google Scholar
White, T. A., Bartesaghi, A., Borgnia, M. J., Meyerson, J. R., De La Cruz, M. J., Bess, J. W., Nandwani, R., Hoxie, J. A., Lifson, J. D., Milne, J. L. & Subramaniam, S. (2010). Molecular architectures of trimeric SIV and HIV-1 envelope glycoproteins on intact viruses: strain-dependent variation in quaternary structure. PLoS Pathogens 6, e1001249.Google Scholar
Winey, M., Mamay, C. L., O'toole, E. T., Mastronarde, D. N., Giddings, T. H. Jr., Mcdonald, K. L. & Mcintosh, J. R. (1995). Three-dimensional ultrastructural analysis of the Saccharomyces cerevisiae mitotic spindle. Journal of Cell Biology 129, 1601–1615.Google Scholar
Winkler, H. (2007). 3D reconstruction and processing of volumetric data in cryo-electron tomography. Journal of Structural Biology 157, 126–137.Google Scholar
Winkler, H. & Taylor, K. A. (2006). Accurate marker-free alignment with simultaneous geometry determination and reconstruction of tilt series in electron tomography. Ultramicroscopy 106, 240–254.Google Scholar
Wolf, M., Garcea, R. L., Grigorieff, N. & Harrison, S. C. (2010). Subunit interactions in bovine papillomavirus. Proceedings of the National Academy of Sciences of the United States of America 107, 6298–6303.Google Scholar
Wright, E. R., Schooler, J. B., Ding, H. J., Kieffer, C., Fillmore, C., Sundquist, W. I. & Jensen, G. J. (2007). Electron cryotomography of immature HIV-1 virions reveals the structure of the CA and SP1 Gag shells. EMBO J 26, 2218–2226.Google Scholar
Xiong, Q., Morphew, M. K., Schwartz, C. L., Hoenger, A. H. & Mastronarde, D. N. (2009). CTF determination and correction for low dose tomographic tilt series. Journal of Structural Biology 168, 378–387.Google Scholar
Yang, Q., Rout, M. P. & Akey, C. W. (1998). Three-dimensional architecture of the isolated yeast nuclear pore complex: functional and evolutionary implications. Molecular Cell 1, 223–234.Google Scholar
Zanetti, G., Riches, J. D., Fuller, S. D. & Briggs, J. A. (2009). Contrast transfer function correction applied to cryo-electron tomography and sub-tomogram averaging. Journal of Structural Biology 168, 305–312.Google Scholar
Zhang, P., Bos, E., Heymann, J., Gnaegi, H., Kessel, M., Peters, P. J. & Subramaniam, S. (2004). Direct visualization of receptor arrays in frozen-hydrated sections and plunge-frozen specimens of E. coli engineered to overproduce the chemotaxis receptor Tsr. Journal of Microscopy 216, 76–83.Google Scholar
Zheng, Q. S., Braunfeld, M. B., Sedat, J. W. & Agard, D. A. (2004). An improved strategy for automated electron microscopic tomography. Journal of Structural Biology 147, 91–101.Google Scholar
Zheng, S. Q., Matsuda, A., Braunfeld, M. B., Sedat, J. W. & Agard, D. A. (2009). Dual-axis target mapping and automated sequential acquisition of dual-axis EM tomographic data. Journal of Structural Biology 168, 323–331.Google Scholar