Nobel prize for chemistry awards 3D electron microscopy

The 2017 Nobel prize for chemistry goes to three scientists for the development of cryo-electron microscopy. The technology makes it possible to examine the structure of large molecules in high resolution.

The resolution of cryo-electron microscopy has increased significantly over the last years. (Source: Martin Högbom/The Royal Swedish Academy of Sciences) -

The three scientists Joachim Frank, Jacques Dubochet and Richard Henderson all contributed to the development of the cryo-electron microscopy. The technology allows the analysis of large biomolecules that cannot be investigated by common x-ray structural analysis. One example for this is RNA polymerase because it cannot be purified in a way that is suitable for x-ray analysis.

Extremly high resolution possible

Cryo-electron microscopy can be used for the investigation of molecules from 20 kDa up to multiple MDa and deliver 3 dimensional structures in a resolution of typically 10 Å to 30 Å. Theoretically, resolutions of 3 Å are possible, however, practical hurdles are interfering with this for the time being.

When using the technique, a sample of the biomolecules, which are dissolved in a 100 nm thin film of water, are instantly frozen to -190 °C using liquid nitrogen cooled ethane. Due to the high cooling speed the water freezes to a jellylike type of ice. This type of ice does not form any crystalline structure that would interfere with the electron beam.

3D images calcualted

In the next step, the electron microscope is used to collect 2D images of the samples. Because of the random orientation of the sample molecules within the ice layer, the 2D images contain information from different angles of the molecules. A computer then analyses the images to calculate a 3-dimensional structure of the molecule. Especially due to rising computing capacity the technology has evolved a lot in recent years.

Joachim Frank was born in Germany and is currently working at the Columbia University in New York. Jacques Dubochet was born in Switzerland and is currently teaching at the university of Lausanne. Richard Henderson, who was born in Scotland, has been working at Cambridge University for some decades.

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