Home Science & Technology A new tool for cryo-electron microscopy

A new tool for cryo-electron microscopy


Microscopic image (top) and structures (bottom) of hemocyanin protein (right) and tobacco mosaic virus (left) using iDPC-STEM. Below are the corresponding 3D structures at 3.5 and 6.5 Å resolution. Author: Forschungszentrum Jülich / Ivan Lazic, Carsten Sachse

Researchers from the Forschungszentrum Jülich and the Heinrich Heine University in Düsseldorf, led by Prof. Dr. Karsten Sachse, use cryo-electron microscopy, or cryo-EM for short, to make biomolecules visible at the atomic level. In an article published now in the journal Methods of nature, they present a new method that combines cryo-EM with a method otherwise used in materials research. The results are also presented and classified in a Nature Briefing.

Still a relatively new technique, cryo-EM has a decisive advantage over X-ray crystallography, which has been routinely used for decades: the building blocks of a protein can be observed in their natural environment in a flash-frozen state without the need to transform them into an artificial crystal beforehand. Cryo-EM is transmission based electron microscopy. On the other hand, an alternative method that researchers are currently using is the further development of scanning transmission electron microscopy with built-in differential phase contrast, or iDPC-STEM for short.

“This method has so far been used primarily in research materials, where this has already resulted in very high resolutions. When rendering biological samplesnow we have directly achieved the quality first made possible by cryo-electron microscopy a few years ago,” says Carsten Sachse, director of the Ernst Rusk Center at Forschungszentrum Jülich and professor at the Heinrich Heine University in Düsseldorf.

Together with research partners from the analytical company Thermo Fischer Scientific in Eindhoven, he was able to map protein structures using iDPC-STEM with a sub-nanometer resolution of 3.5 angstroms. “Cryo-electron microscopy today is a bit more advanced in comparison. But our results show that iDPC-STEM is in principle capable, with some optimization, of achieving resolution similar to state-of-the-art cryo-EM and expanding the possibilities for structural analysis; especially for very heterogeneous, inhomogeneous samples or individual particles, when averaging options are limited,” says Carsten Sachs.

A new tool for cryo-electron microscopy

Artist’s rendering of a scanning transmission electron microscopy (STEM) approach: a small raster of an electron beam over a sample in small increments to illuminate snap-frozen biomolecules in ice. Credit: Forschungszentrum Jülich / Daniel Mann, Carsten Sachse

In conventional cryo-electron microscopy, thousands, sometimes tens or hundreds of thousands, of images of the sample are taken from different angles. A powerful computer uses these images to calculate a detailed three-dimensional model of the molecule or particle. Scanning electron microscopy, on the other hand, scans objects line by line in small increments to produce a composite image that, like conventional cryo-EM, serves as the basis for calculating the three-dimensional structure. As in cryo-electron microscopy, a low-dose electron beam is used because biomolecules are usually very sensitive. This prevents the high energy of the beam from destroying sensitive structures.

Electron cryomicroscopy: using low-cost technology to produce high-resolution images

Additional information:
Ivan Lazic et al., Single-particle cryo-EM structures with iDPC–STEM at near atomic resolution, Methods of nature (2022). DOI: 10.1038/s41592-022-01586-0

Obtaining cryo-EM structures using scanning transmission electron microscopy, Methods of nature (2022). DOI: 10.1038/s41592-022-01587-z

Citation: A New Tool for Cryo-Electron Microscopy (2022, September 7) Retrieved September 7, 2022, from https://phys.org/news/2022-09-tool-cryo-electron-microscopy.html

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