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Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for...
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In 1931, physicist Ernst Ruska—building on the idea that magnetic fields can direct an electron beam just as lenses can direct a beam of light in an optical microscope—developed the first prototype of the electron microscope. This development led to the development of the field of electron microscopy. In the transmission electron microscope (TEM), electrons are produced by a hot tungsten element and accelerated by a potential difference in an electron gun, which gives them up to 400...
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Generalized single-particle cryo-EM--a historical perspective.

Joachim Frank1

  • 1HHMI, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA Department of Biological Sciences, Columbia University, New York, NY, USA jf2192@cumc.columbia.edu.

Microscopy (Oxford, England)
|November 15, 2015
PubMed
Summary
This summary is machine-generated.

Single-particle cryo-electron microscopy (cryo-EM) has a history dating back to the 1970s. Advances in digital cameras now enable near-atomic resolution for smaller biological molecules.

Keywords:
3D reconstructionimage processingmolecular structureribosome

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Area of Science:

  • Structural biology
  • Biophysics
  • Biochemistry

Background:

  • Review of the historical development of single-particle cryo-electron microscopy (cryo-EM) for biological molecules without internal symmetry.
  • Focus on the mathematical and computational methodologies underpinning the technique's evolution.

Observation:

  • The field of cryo-EM is undergoing a significant transformation.
  • Introduction of direct electron detectors (digital cameras) capable of single electron counting.

Findings:

  • Near-atomic resolution is now achievable for smaller biological molecules using cryo-EM.
  • Mathematical and computational advancements have been crucial to cryo-EM's progress.

Implications:

  • Enables high-resolution structural determination of previously challenging biomolecules.
  • Accelerates understanding of molecular mechanisms in biology and disease.
  • Opens new avenues for drug discovery and molecular design.