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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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Updated: Mar 15, 2026

Do's and Don'ts of Cryo-electron Microscopy: A Primer on Sample Preparation and High Quality Data Collection for Macromolecular 3D Reconstruction

Do's and Don'ts of Cryo-electron Microscopy: A Primer on Sample Preparation and High Quality Data Collection for Macromolecular 3D Reconstruction

Published on: January 9, 2015

High-Resolution Macromolecular Structure Determination by MicroED, a cryo-EM Method.

J A Rodriguez¹, T Gonen²

¹UCLA-DOE Institute, University of California, Los Angeles CA, United States.

Methods in Enzymology

|August 31, 2016

Summary

This summary is machine-generated.

Microcrystal electron diffraction (MicroED) enables atomic-resolution macromolecular structure determination from tiny crystals. This cryo-electron microscopy technique enhances accessibility for researchers in structural biology.

Keywords:

Crystal Crystallography Diffraction Electron MicroED Protein cryo-EM

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Area of Science:

Structural Biology
Biophysics
Materials Science

Background:

Cryo-electron microscopy (cryo-EM) is advancing macromolecular structure determination.
Microcrystal electron diffraction (MicroED) is an emerging cryo-EM technique.
Atomic resolution is achievable from very small 3D crystals.

Purpose of the Study:

To review the principles and practical applications of MicroED.
To provide context for electron microscopists and crystallographers.
To highlight key considerations for performing MicroED experiments.

Main Methods:

Microcrystal electron diffraction (MicroED) utilizes a focused electron beam.
Data collection from 3D crystals, often less than a few hundred nanometers thick.
Structure determination through diffraction pattern analysis.

Main Results:

MicroED allows for atomic resolution structure determination.
The technique is effective for extremely small crystals.
It complements traditional X-ray crystallography.

Conclusions:

MicroED is a powerful tool for macromolecular structure determination.
It expands the scope of samples amenable to high-resolution analysis.
This method contributes to the broader accessibility of cryo-EM techniques.