Cryo-electron microscopy

The 2017 Nobel Prize in chemistry has been awarded to three scientists for improving images made of biological molecules. Jacques Dubochet, Joachim Frank and Richard Henderson will share the nine million kronor (£831,000) prize.

They were named at a press conference in Stockholm, Sweden. They developed a technique called cryo-electron microscopy (cryo-EM), which simplifies the process for looking at the machinery of life. The process makes it possible for life's molecular building blocks to be captured mid-movement and allowed scientists to visualise processes that had never before been seen.

Transmission electron microscopes (TEMs) use a beam of electrons to examine the structures of molecules and materials at the atomic scale. As the beam passes through a very thin sample, it interacts with the molecules, which projects an image of the sample onto the detector (often a charge-couple device; CCD). Because the wavelength of electrons is much shorter than that of light, it can reveal much finer detail than even super-resolution light microscopy (which was awarded the chemistry Nobel prize in 2014), writes www.chemistryworld.com.

But some materials – particularly biomolecules – are not compatible with the high-vacuum conditions and intense electron beams used in traditional Transmission electron microscopes (TEMs). The water that surrounds the molecules evaporates, and the high energy electrons burn and destroy the molecules. Cryo-EM uses frozen samples, gentler electron beams and sophisticated image processing to overcome these problems.

X-ray diffraction can give very high resolution structures of biomolecules, and several Nobel prizes have been awarded for just that. But to get an x-ray structure, you need to be able to crystallise the molecule. Many proteins won’t crystallise at all. And in some cases, the process of crystallisation alters the structure, so it’s not representative of what the molecule looks like in real life, explains chemistryworld.com.

Cryo-EM doesn’t require crystals, and it also enables scientists to see how biomolecules move and interact as they perform their functions, which is much more difficult using crystallography. NMR can also give very detailed structures, and investigate conformational changes or binding of small molecules.

But it’s limited to relatively small proteins or parts of proteins, and usually soluble intracellular proteins, rather than those embedded in cell membranes. If you want to study larger proteins, membrane-bound receptors, or complexes of several biomolecules together, cryo-EM is where it’s at, the website adds.