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Electron tomography of cells

  • Lu Gan (a1) and Grant J. Jensen (a1) (a2)

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.

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*Author for correspondence: G. J. Jensen. Tel.: (626) 395 – 8827; Fax: (626) 395 – 5730; Email:
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Adrian M., Dubochet J., Lepault J. & Mcdowall A. W. (1984). Cryo-electron microscopy of viruses. Nature 308, 3236.
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, 35833588.
Al-Amoudi A., Diez D. C., Betts M. J. & Frangakis A. S. (2007). The molecular architecture of cadherins in native epidermal desmosomes. Nature 450, 832837.
Alon U., Surette M. G., Barkai N. & Leibler S. (1999). Robustness in bacterial chemotaxis. Nature 397, 168171.
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, 260275.
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, 13871390.
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, 611615.
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, 817823.
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, 7792.
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, 577588.
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), 693701.
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, 13081313.
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, 8891.
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, 4553.
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, 560569.
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, 514.
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, 3041.
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), 1718117186.
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, 1520.
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, 59645970.
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), 329339.
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, 731740.
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, 29722981.
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.
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, 67396745.
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, 13111328.
Clermont Y., Rambourg A. & Hermo L. (1995). Trans-Golgi network (TGN) of different cell types: three-dimensional structural characteristics and variability. Anatomical Record 242, 289301.
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, 9194.
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, 319340.
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, 312325.
Danev R. & Nagayama K. (2008). Single particle analysis based on Zernike phase contrast transmission electron microscopy. Journal of Structural Biology 161, 211218.
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, 674684.
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, 157168.
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, 141151.
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, 225228.
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, 129228.
Dubochet J., Mcdowall A. W., Menge B., Schmid E. N. & Lickfeld K. G. (1983). Electron microscopy of frozen-hydrated bacteria. Journal of Bacteriology 155, 381390.
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, 385406.
Erickson H. P. (1997). FtsZ, a tubulin homologue in prokaryote cell division. Trends in Cell Biology 7, 362367.
Fan G. Y., Mercurio P. J., Young S. J. & Ellisman M. H. (1993). Telemicroscopy. Ultramicroscopy 52, 499503.
Fernandez J. J., Li S. & Crowther R. A. (2006). CTF determination and correction in electron cryotomography. Ultramicroscopy 106, 587596.
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, 13211332.
Forster F. (2005). Quantitative Analysis of Macromolecules in Cryoelectron Tomograms using Correlation Methods. Technical University of Munich, Munich, Germany.
Frangakis A. S. & Hegerl R. (2001). Noise reduction in electron tomographic reconstructions using nonlinear anisotropic diffusion. Journal of Structural Biology 135, 239250.
Frank J. (2006). Electron Tomography: Methods for Three-Dimensional Visualization of Structures in the Cell, 2nd edn. London, New York: Springer.
Frederik P. M. & Hubert D. H. (2005). Cryoelectron microscopy of liposomes. Methods in Enzymology 391, 431448.
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, 15791586.
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, 503507.
Gan L., Ladinsky M. S. & Jensen G. J. (2011). Organization of the smallest eukaryotic spindle. Current Biology 21, 15781583.
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, 222225.
Gilbert P. (1972). Iterative methods for the three-dimensional reconstruction of an object from projections. Journal of Theoretical Biology 36, 105117.
Gilkey J. C. & Staehelin L. A. (1986). Advances in ultrarapid freezing for the preservation of cellular ultrastructure. Journal of Electron Microscopy Technique 3, 177210.
Gitai Z. (2005). The new bacterial cell biology: moving parts and subcellular architecture. Cell 120, 577586.
Goodsell D. S. (2005). Visual methods from atoms to cells. Structure 13, 347354.
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, 13961398.
Gruska M., Medalia O., Baumeister W. & Leis A. (2008). Electron tomography of vitreous sections from cultured mammalian cells. Journal of Structural Biology 161, 384392.
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, 1912319127.
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, 180190.
He W., Cowin P. & Stokes D. L. (2003). Untangling desmosomal knots with electron tomography. Science 302, 109113.
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, 103113.
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, 542546.
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.
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, 899929.
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, 132.
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, 232242.
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, 14831487.
Hsieh C. E., Marko M., Frank J. & Mannella C. A. (2002). Electron tomographic analysis of frozen-hydrated tissue sections. Journal of Structural Biology 138, 6373.
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, 105117.
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, 28132819.
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, 288297.
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, 231240.
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, 739746.
Jones L. J., Carballido-Lopez R. & Errington J. (2001). Control of cell shape in bacteria: helical, actin-like filaments in Bacillus subtilis. Cell 104, 913922.
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, 1894418949.
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, 68056810.
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, 1655516560.
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, 242245.
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, 276308.
Kremer J. R., Mastronarde D. N. & Mcintosh J. R. (1996). Computer visualization of three-dimensional image data using IMOD. Journal of Structural Biology 116, 7176.
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, 5461.
Kurner J., Frangakis A. S. & Baumeister W. (2005). Cryo-electron tomography reveals the cytoskeletal structure of Spiroplasma melliferum. Science 307, 436438.
Ladinsky M. S. & Howell K. E. (2007). Electron tomography of immunolabeled cryosections. Methods in Cell Biology 79, 543558.
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, 11351149.
Ladinsky M. S., Pierson J. M. & Mcintosh J. R. (2006). Vitreous cryo-sectioning of cells facilitated by a micromanipulator. Journal of Microscopy 224, 129134.
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, 144167.
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, 221227.
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, 649659.
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, 119132.
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), 46944708.
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, 10381043.
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, 50265036.
Lucic V., Forster F. & Baumeister W. (2005). Structural studies by electron tomography: from cells to molecules. Annual Review of Biochemistry 74, 833865.
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, 213226.
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, 977991.
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, 215217.
Marsh B. J. (2007). Reconstructing mammalian membrane architecture by large area cellular tomography. Methods in Cell Biology 79, 193220.
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, 23992406.
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, 55655570.
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), 461468.
Mastronarde D. N. (1997). Dual-axis tomography: an approach with alignment methods that preserve resolution. Journal of Structural Biology 120, 343352.
Mastronarde D. N. (2005). Automated electron microscope tomography using robust prediction of specimen movements. Journal of Structural Biology 152, 3651.
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, 221222.
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, 273281.
Mcdonald K. L. & Auer M. (2006). High-pressure freezing, cellular tomography, and structural cell biology. Biotechniques 41, 137143.
Mcewen B. F., Downing K. H. & Glaeser R. M. (1995). The relevance of dose-fractionation in tomography of radiation-sensitive specimens. Ultramicroscopy 60, 357373.
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, 90409044.
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, 322333.
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, 93129.
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, 401413.
Mcmullan G., Clark A. T., Turchetta R. & Faruqi A. R. (2009). Enhanced imaging in low dose electron microscopy using electron counting. Ultramicroscopy 109, 14111416.
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, 12091213.
Mercogliano C. P. & Derosier D. J. (2007). Concatenated metallothionein as a clonable gold label for electron microscopy. Journal of Structural Biology 160, 7082.
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.
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, 152159.
Milne J. L. & Subramaniam S. (2009). Cryo-electron tomography of bacteria: progress, challenges and future prospects. Nature Reviews Microbiology 7, 666675.
Minton A. P. (2006). How can biochemical reactions within cells differ from those in test tubes? Journal of Cell Science 119, 28632869.
Moor H. (1987). Theory and Practice of High Pressure Freezing. Berlin: Springer-Verlag.
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, 365370.
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, 263267.
Murphy G. E. & Jensen G. J. (2005). Electron cryotomography of the E. coli pyruvate and 2-oxoglutarate dehydrogenase complexes. Structure 13, 17651773.
Murphy G. E., Leadbetter J. R. & Jensen G. J. (2006). In situ structure of the complete Treponema primitia flagellar motor. Nature 442, 10621064.
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, 125132.
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, 11841195.
Nagayama K. & Danev R. (2009). Phase-plate electron microscopy: a novel imaging tool to reveal close-to-life nano-structures. Biophysical Reviews 1, 3742.
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), 227234.
Nickell S., Kofler C., Leis A. P. & Baumeister W. (2006). A visual approach to proteomics. Nature Reviews Molecular Cell Biology 7, 225230.
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, 298313.
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, 451456.
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, 20172031.
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, 498500.
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, 613621.
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, 334341.
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, 23752379.
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, 909915.
Penczek P. A. (2010a). Fundamentals of three-dimensional reconstruction from projections. Methods in Enzymology 482, 133.
Penczek P. A. (2010b). Image restoration in cryo-electron microscopy. Methods in Enzymology 482, 3572.
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, 16051612.
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, 219225.
Pilhofer M., Ladinsky M. S., Mcdowall A. W. & Jensen G. J. (2010). Bacterial TEM: new insights from cryo-microscopy. Methods in Cell Biology 96, 2145.
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, 277287.
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, 169179.
Salje J., Zuber B. & Lowe J. (2009). Electron cryomicroscopy of E. coli reveals filament bundles involved in plasmid DNA segregation. Science 323, 509512.
Sandberg K. & Brega M. (2007). Segmentation of thin structures in electron micrographs using orientation fields. Journal of Structural Biology 157, 403415.
Saxton W. O., Baumeister W. & Hahn M. (1984). Three-dimensional reconstruction of imperfect two-dimensional crystals. Ultramicroscopy 13, 5770.
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, 110114.
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, 15631572.
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, 98109.
Seybert A., Herrmann R. & Frangakis A. S. (2006). Structural analysis of Mycoplasma pneumoniae by cryo-electron tomography. Journal of Structural Biology 156, 342354.
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, 19411974.
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), 78657870.
Sigworth F. J. (1998). A maximum-likelihood approach to single-particle image refinement. Journal of Structural Biology 122, 328339.
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, 560564.
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, 230243.
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.
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, 74507463.
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, 1118.
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, 650655.
Tang H., Braun T. F. & Blair D. F. (1996). Motility protein complexes in the bacterial flagellar motor. Journal of Molecular Biology 261, 209221.
Taylor K. A. & Glaeser R. M. (1974). Electron diffraction of frozen, hydrated protein crystals. Science 186, 10361037.
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, 64046412.
Tocheva E. I., Li Z. & Jensen G. J. (2010). Electron cryotomography. Cold Spring Harbor Perspectives in Biology 2, a003442.
Tokuyasu K. T. (1986). Application of cryoultramicrotomy to immunocytochemistry. Journal of Microscopy 143, 139149.
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, 10711081.
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, 429435.
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, 196204.
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, 12171223.
Volkmann N. (2002). A novel three-dimensional variant of the watershed transform for segmentation of electron density maps. Journal of Structural Biology 138, 123129.
Wang Q., Mercogliano C. P. & Lowe J. (2011). A ferritin-based label for cellular electron cryotomography. Structure 19, 147154.
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, 211218.
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, 1340.
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.
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, 16011615.
Winkler H. (2007). 3D reconstruction and processing of volumetric data in cryo-electron tomography. Journal of Structural Biology 157, 126137.
Winkler H. & Taylor K. A. (2006). Accurate marker-free alignment with simultaneous geometry determination and reconstruction of tilt series in electron tomography. Ultramicroscopy 106, 240254.
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, 62986303.
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, 22182226.
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, 378387.
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, 223234.
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, 305312.
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, 7683.
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, 91101.
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, 323331.
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