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Cryo-electron Microscopy

Cryo-electron Microscopy

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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Transmission electron microscopy (TEM) can be used to determine the 3D structure of biological samples with the help of techniques such as electron microscope tomography and single-particle reconstruction. While single-particle reconstruction can examine macromolecules and macromolecular complexes in vitro conditions only, tomography permits the study of cell components or small cells in vivo.
Electron Tomography
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Related Experiment Video

Updated: Oct 15, 2025

Electron Cryotomography of Bacterial Cells

Electron Cryotomography of Bacterial Cells

Published on: May 6, 2010

Conquer by cryo-EM without physically dividing.

Gabriel C Lander¹, Robert M Glaeser²

¹Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, U.S.A.

Biochemical Society Transactions

|October 28, 2021

Summary

This summary is machine-generated.

Single-particle cryo-electron microscopy (cryo-EM) now achieves high-resolution structures for small proteins (<100 kDa). Focused refinement techniques like masking and refining improve resolution for specific regions within larger structures.

Keywords:

cryo-electron microscopy divide and conquer structure determination

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Area of Science:

Structural Biology
Biophysics
Biochemistry

Background:

Single-particle cryo-electron microscopy (cryo-EM) has advanced significantly.
High-resolution structure determination of small macromolecules (<100 kDa) is increasingly feasible.

Purpose of the Study:

To review progress in cryo-EM for small particles.
To discuss the potential and limitations of focused refinement techniques.
To compare experimental results with theoretical estimates for small particle reconstruction.

Main Methods:

Review of recent advancements in single-particle cryo-EM.
Explanation of focused refinement strategies, including masking and refining.
Comparison of experimental data with theoretical models.

Main Results:

Substantial progress has been made in determining high-resolution structures of macromolecules smaller than 100 kDa using cryo-EM.
Focused refinement, or 'masking and refining,' allows for high-resolution analysis of specific regions within larger complexes.
A gap persists between theoretical predictions and experimental achievements for the smallest reconstructible particle sizes.

Conclusions:

Cryo-EM is a powerful tool for small macromolecule structure determination.
Focused refinement offers a 'divide and conquer' approach within the native context.
Further improvements in equipment and methods are needed to bridge the gap between theoretical and experimental limits for small particle resolution.