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Related Concept Videos

Cryo-electron Microscopy01:28

Cryo-electron Microscopy

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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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Electron Microscope Tomography and Single-particle Reconstruction01:07

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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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Updated: Feb 27, 2026

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

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Structure first - exploration and discovery with cryo-electron microscopy.

Miguel Ricardo Leung1

  • 1Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.

Journal of Cell Science
|February 26, 2026
PubMed
Summary
This summary is machine-generated.

Cryo-electron microscopy (cryo-EM) enables a structure-first approach for molecular discovery. This technique helps identify unknown proteins and interactions, expanding structural biology

Keywords:
De novo protein identificationCryo-electron microscopyCryo-electron tomography

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Area of Science:

  • Structural Biology
  • Molecular Biology
  • Biophysics

Background:

  • Direct observation of living systems fuels biological discovery.
  • Cryo-electron microscopy (cryo-EM) offers high-resolution structural analysis.
  • Advancements have increased cryo-EM throughput, robustness, and accessibility.

Purpose of the Study:

  • To highlight cryo-electron microscopy's role in a structure-first discovery approach.
  • To showcase cryo-EM's capability in analyzing diverse biological samples.
  • To emphasize cryo-EM's potential for identifying novel proteins and interactions.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) for high-resolution structural analysis.
  • Machine learning-assisted model building for cryo-EM maps.
  • Proteomics and cross-linking mass spectrometry for protein identification.

Main Results:

  • Cryo-EM now analyzes native protein complexes and in-situ cellular structures.
  • Unknown proteins are increasingly identified in cryo-EM studies.
  • Molecular identity can be derived from cryo-EM maps without prior knowledge or labeling.

Conclusions:

  • Cryo-EM facilitates a structure-first approach for molecular exploration.
  • Structural biology now extends to discovering novel proteins and interactions.
  • Cryo-EM is a powerful tool for uncovering the molecular basis of biological processes.