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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...

Electron Microscope Tomography and Single-particle Reconstruction

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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
Electron tomography can be performed either in TEM or STEM (scanning transmission...

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Related Experiment Video

Updated: Aug 24, 2025

Cryo-EM and Single-Particle Analysis with Scipion

Cryo-EM and Single-Particle Analysis with Scipion

Published on: May 29, 2021

Progress in spatial resolution of structural analysis by cryo-EM.

Yoshiyuki Fukuda¹, Kevin Stapleton², Takayuki Kato²

¹Department of Cell Biology and Anatomy, Graduate School of Medicine, The University of Tokyo, Bunkyo, Tokyo 113-0033, Japan.

Microscopy (Oxford, England)

|October 21, 2022

Summary

This summary is machine-generated.

Electron cryomicroscopy (cryo-EM) now provides high-resolution structures of large biomolecules, accelerating structure-based drug discovery. Technological advances have made cryo-EM a key method for determining macromolecular structures.

Keywords:

cryo-EM cryo-electron tomography high resolution single particle analysis subtomogram averaging

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A Robust Single-Particle Cryo-Electron Microscopy cryo-EM Processing Workflow with cryoSPARC, RELION, and Scipion

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Last Updated: Aug 24, 2025

Cryo-EM and Single-Particle Analysis with Scipion

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Published on: May 29, 2021

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Published on: January 31, 2022

Area of Science:

Structural biology
Biochemistry
Drug discovery

Background:

High-resolution structural information is crucial for structure-based drug design.
Electron cryomicroscopy (cryo-EM) has revolutionized structural biology.
Previously, cryo-EM yielded low-resolution structures, limiting its application.

Approach:

This review details the evolution of cryo-EM techniques, including single particle analysis and tomography.
Focus is placed on technological innovations driving high-resolution reconstructions.
The integration of new camera technology, software, and algorithms is highlighted.

Key Points:

Cryo-EM now enables analysis of large macromolecular complexes in various functional states.
Dramatic improvements in achievable resolution are due to technological advancements.
Cryo-EM has become a primary method for structure determination in structural biology.

Conclusions:

Cryo-EM is now indispensable for high-resolution structural analysis of biological macromolecules.
The technique plays a significant role in the structure-based drug discovery pipeline.
Future prospects indicate cryo-EM will remain a dominant method in structural biology.