There’s an old joke that you can’t trust atoms — they make up everything. But until fairly recently, there was no real way to see individual atoms. You could infer things about them using X-ray crystallography or measure their pull on tiny probes using atomic force microscopes, but not take a direct image. Until now. Two laboratories recently used cryo-electron microscopy to directly image atoms in a protein molecule with a resolution of about 1.2 x 10-7 millimeters or 1.2 ångströms. The previous record was 1.54 ångströms.
Recent improvements in electron beam technology helped, as did a device that ensures electrons that strike the sample travel at nearly the same speeds. The latter technique resulted in images so clear, researchers could identify individual hydrogen atoms in the apoferritin molecule and the water surrounding it.
For years, the standard way to study protein structure was to form a crystal and study the way that crystal diffracts X-rays. However, some proteins are difficult or even impossible to crystalize. Cryo-electron microscopy doesn’t have this issue. The microscope operator has to flash freeze the sample. A better understanding of protein structure can further research into things such as enzyme action and help scientists develop better drugs.
Computer analysis of the electron emissions is a key part of the technique as well and one of the scientists involved believes that resolutions below 1 ångström are probably not possible for this method with current computing power. In addition, the quality of the image depends partially on the stability of the protein. Apoferritin is highly stable, but some other molecules they tested are not that stable. That means X-ray crystallography will probably remain the method of choice for proteins that will easily crystalize. This is especially true since the cryo-electron microscopy method can take hours or days of data collection to form a complete image.