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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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Related Experiment Video

Updated: Aug 27, 2025

Single-Molecule Imaging of Lateral Mobility and Ion Channel Activity in Lipid Bilayers using Total Internal Reflection Fluorescence TIRF Microscopy

Single-Molecule Imaging of Lateral Mobility and Ion Channel Activity in Lipid Bilayers using Total Internal Reflection Fluorescence TIRF Microscopy

Published on: February 17, 2023

Studying membrane modulation mechanisms by electron cryo-tomography.

Davide Zabeo¹, Karen M Davies¹

¹Diamond Light Source, Harwell Science and Innovation Campus, Didcot, UK.

Current Opinion in Structural Biology

|September 29, 2022

Summary

Electron cryo-tomography reveals how cells shape membranes for vital functions. This advanced imaging technique overcomes challenges in studying dynamic protein assemblies, aiding disease research.

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Last Updated: Aug 27, 2025

Single-Molecule Imaging of Lateral Mobility and Ion Channel Activity in Lipid Bilayers using Total Internal Reflection Fluorescence TIRF Microscopy

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Area of Science:

Cellular biology
Structural biology
Biophysics

Background:

Membrane modulation is essential for cellular processes like energy production, division, trafficking, and pathogen entry.
Defects in membrane modulation are linked to various diseases.
Studying the dynamic, multi-conformation protein assemblies involved in membrane modulation is challenging.

Purpose of the Study:

To review the application of electron cryo-tomography (cryo-ET) in elucidating molecular mechanisms of membrane modulation.
To highlight how cryo-ET addresses the dynamic nature of macromolecular assemblies.

Main Methods:

Electron cryo-tomography (cryo-ET) provides high-resolution (nanometre to sub-nanometre) imaging of cellular structures.
Subtomogram averaging is used to analyze the conformations of macromolecular assemblies.

Main Results:

Cryo-ET enables visualization of complex macromolecular assemblies within intact cells.
The technique allows for the study of dynamic conformational changes crucial for membrane shaping.
Advances in cryo-ET are resolving previous limitations in studying membrane modulation mechanisms.

Conclusions:

Electron cryo-tomography is a powerful tool for uncovering the molecular basis of membrane modulation.
This technology facilitates a deeper understanding of cellular membrane dynamics and associated diseases.