History of the Electron Microscope in Cell Biology


In the years following World War II there was an explosion in the biological sciences with the rapid emergence of cell biology, molecular biology and biophysics. These events were affected by the development and use of new technologies for cellular fractionation and imaging, specifically the electron microscope, which provided a resolution, that is, unobtainable with light microscopes. Electron microscopes made visible the fine structure of cells and their organelles, the structure of viruses. Now cryo‐electron microscopy is emerging as a key tool to visualize and localize the proteins in an entire cell, the organization of actin filaments in the cytoskeleton, and molecular complexes such as nuclear pores.

Keywords: transmission electron microscope; scanning electron microscope; cryo‐electron microscopy; cell ultrastructure; structural biology

Figure 1.

TEM of mouse cerebellum. v, neurotransport vesicles; m, mitochondria; my, myelin sheath; n, nerve fibre and sj, synaptic junction. Magnification bar equals 500 nm. Image obtained by Nicki Watson, Whitehead Institute, Massachusetts Institute of Technology and reproduced with permission.

Figure 2.

TEM of cultured cell line. Mouse 3T3 control cells. m, mitochondria; n, nucleus; G, Golgi complex; np, nuclear pores and er, endoplasmic reticulum. Magnification bar equals 500 nm. Image obtained by Nicki Watson, Whitehead Institute, Massachusetts Institute of Technology and reproduced with permission.

Figure 3.

TEM of mouse skeletal muscle. A, A‐band; M, M‐line; Z, Z‐disk; I, I‐band; H, H‐band; m, mitochondria; Sr, sarcoplasmic reticulum and Ts, T‐system. Magnification bar equals 500 nm. Image obtained by Nicki Watson, Whitehead Institute, Massachusetts Institute of Technology and reproduced with permission.



Abbe E (1873) Beiträge zur Theorie des Mikroskops und der mikroskopischen Wahrnehmung. Archiv für mikroskopische Anatomie 9: 413–468.

Airy GB (1835) On the diffraction of an object‐glass with circular aperture. Transactions of the Cambridge Philosophical Society 5: 283–291.

von Ardenne M (1938) The scanning electron microscope. Practical realization (in German). Zeitschrift für Physik. 19: 407–416.

von Ardenne M (1940) Elektronen‐Übermikroskopie, Physik, Technik, Ergebnisse. Berlin: Verlag von Julius Springer.

Baumeister W Max Planck Institute of Biochemistry. Department of Molecular Structural Biology. http://www.biochem.mpg.de/baumeister/index.html. Accessed on 3 October 2008.

Bennett MR (2001) History of the Synapses. Boca Raton, FL: CRC Press.

von Borries B (1940) High resolution images fro the electron microscope used in reflection (in German). Zeitschrift für Physik 116: 370–378.

Braun F (1897) Ueber ein Verfahren zur Demonstration und zum Studium des zeitlichen Verlaufes variabler Ströme [On a technique for the demonstration and for the study of the course of variable currents]. Annalen der Physik und Chemie (Leipzig), Band 60: 552–559.

Cajal SR (1906) The structure and connexions of neurons. Nobel Lecture, 12 December. http://nobelprize.org/nobel_prizes/medicine/laureates/1906/cajal‐lecture.html. Accessed on 12 September 2008.

Dubochet J and McDowall AW (1981) Vitrification of pure water for electron microscopy. Journal of Microscopy 124: RP3–RP4.

Glaeser RM (2008) Cryo‐electron microscopy of biological nanostructures. Physics Today 61: 48–54.

Golgi C (1906) The neuron doctrine‐theory and facts. Nobel Lecture, 11 December. http://nobelprize.org/nobel_prizes/medicine/laureates/1906/golgi‐lecture.html. Accessed on 12 September 2008.

Golgi G (1898) On the structure of nerve cells (Translated by NG Lipsky). Journal of Microscopy 155: 3–7.

Gruska M, Medalia O, Baumeister W and Leis A (2008) Electron tomography of vitreous sections from cultured mammalian cells. Journal of Structural Biology 161: 384–392.

Hawkes PW and Spence JCH (2007) Science of Microscopy, vol. 1. New York: Springer.

Knoll M and Ruska E (1932) Das Elektronenmikroskop. Zeitschrift für Physik 78: 318–339.

Lemmerich J and Spring H (1980) Three Centuries of Microscopes and Cell Biology. Heidelberg: European Cell Biology Organization.

Masters BR (2007) Ernst Abbe and the Foundation of Scientific Microscopes. Optics and Photonics News 18: 18–23. Optical Society of America, Washington DC.

Masters BR (2008) History of the optical microscope in cell biology and medicine. Encyclopedia of Life Sciences (ELS). DOI: 10.1002/9780470015902.a0003082. Chichester UK: Wiley.

Mazzarello P and Bentivoglio M (1998) The centenarian Golgi apparatus. Nature 392: 543–544.

McMullan D (1988) Von Ardenne and the scanning electron microscope. Proceedings of the Royal Microscopical Society 23: 283–288.

McMullan D (1989) SEM‐past, present and future. Journal of Microscopy 155: 373–392.

Mulvey T (1989) The electron microscope: the British contribution. Journal of Microscopy 155: 327–338.

Nickell S, Mihalache O, Beck F et al. (2007) Structural analysis of the 26S proteasome by cryoelectron tomography. Biochemical and Biophysical Research Communications 353: 115–120.

Ortiz JO, Förster F, Kürner J et al. (2006) 70S ribosomes in intact cells by cryoelectron tomography and pattern recognition. Journal of Structural Biology 156: 334–341.

Palade GE (1974) Intracellular aspects of the process of protein secretion. Nobel Lecture, 12 December. http://nobelprize.org/nobel_prizes/medicine/laureates/1974/palade‐lecture.pdf. Accessed on 21 August 2008.

Porter KR, Claude A and Fullam (1945) A study of tissue culture cells by electron microscopy. Journal of Experimental Medicine 81(3): 233–246.

Rayleigh L (1896) On the theory of optical images with special reference to the microscope. The London, Edinburgh, and Dublin Philosophical Magazine and Journal of Science 42: 167–195.

Robinson JD (2001) Mechanisms of Synaptic Transmission, Bridging the Gaps (1890–1990). New York: Oxford University Press.

Rockefeller University at their Web site, Celebrating 50 Years of Electron Microscopy and Modern Cell Biology, Journey in to the Cell. http://www.rockefeller.edu/rucal/journey/journey.html. Accessed on 5 September 2008.

Ruska E (1980) The Early Development of Electron Lenses and Electron Microscopy. (Translated by Tom Mulvey). Stuttgart: Hirzel Verlag.

Ruska E (1986) The development of the electron microscope and of electron microscopy. Nobel Lecture, 8 December. http://nobelprize.org/nobel_prizes/physics/laureates/1986/ruska‐lecture.pdf. Accessed on 21 August 2008.

Santini M (1975) Golgi Centennial Symposium: Perspectives in Neurobiology. New York: Raven Press.

Sartori A, Gatz R, Beck F et al. (2007) Correlative microscopy: bridging the gap between fluorescence light microscopy and cryo‐electron tomography. Journal of Structural Biology 160(2): 135–145.

Slayter EM and Slayter HS (1992) Light and Electron Microscopy. Cambridge: Cambridge University Press.

Williams DB and Carter CB (1996) Transmission Electron Microscopy, Four Volumes. New York: Plenum Press.

Zworykin VA, Hillier J and Snyder RL (1942) A scanning electron microscope. ASTM Bull 117: 15–23.

Further Reading

Fawcett DW (1966) An Atlas of Fine Structure, The Cell, Its Organelles and Inclusions. Philadelphia: W. B. Saunders Company.

Freundlich MM (1994) The history of the development of the first high‐resolution electron microscope. Remembering the Knoll Research Team at the Technical University, Berlin, 1927–1934. MSA Bulletin 24: 405–415.

Haguenau F, Hawkes PW, Hutchison JL et al. (2003) Key events in the history of electron microscopy. Microscopy and Microanalysis 9: 96–138.

McMullan D (1995) Scanning electron microscopy 1928–1965. Scanning 17: 175–185.

Newberry SP (1993) Early electron microscopy remembered through the candlelight of history. MSA Bulletin 23: 146–152.

Plitzko JM and Baumeister W (2007) Cryoelectron tomography (CET). In: Hawkes PW and Spence JCH (eds) Science of Microscopy, vol. I, pp. 535–604. New York: Springer.

Rasmussen N (1997) Picture Control, the Electron Microscope and the Transformation of Biology in America 1940–1960. Stanford: Stanford University Press.

The Cathode Ray Tube Web site: http://members.chello.nl/∼h.dijkstra19/index.html. Accessed on 22 September 2008.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Masters, Barry R(Sep 2009) History of the Electron Microscope in Cell Biology. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021539]