Cryo-Electron Microscopy: Advanced Version of Microscopy

Cryo-Electron Microscopy (Cryo-EM) is an advanced form of microscopy that allows observation of tiny specimens in their natural environment.  It is also known as electron cryomicroscopy. It is an advanced version of transmission electron microscopy (TEM).

What is microscopy?

Microscopy is the study of tiny objects and specimens that cannot be seen with the naked eye by employing microscopes.  The development of microscopy revolutionized many branches of science like biology, histology, biochemistry and physical sciences. Optical, electron, and scanning probe microscopy are the three major branches of microscopy. 

Optical microscopy and electron microscopy use principles of diffraction, reflection, or refraction of electromagnetic radiation or electron beams falling on the tiny object. The scattered radiation or beam is collected to create an image of the tiny object. Scanning probe microscopy uses the interaction of a scanning probe with the surface of the tiny object.  

What is transmission electron microscopy?

Transmission electron microscope (TEM) employs a beam of electrons to study the structures of molecules and tiny objects of atomic scale.  The wavelength of an electron beam is much shorter than the wavelength of a light beam. Hence electron beam is capable of creating much better image. A charge couple device, CCD, acts as a detector in this process.  When the beam passes through the object under observation, the interaction with the molecule projects an image of the specimen onto the detector. The inventors of TEM won the chemistry Nobel prize in 2014.

But some specimens like biomolecules cannot be subjected to study under transmission electron microscopy due to the intensity of electron beams which often evaporates the water that surrounds the molecules which leads to burn and damage of the molecules.

What is x-ray diffraction or NMR?

X-ray diffraction is another method used for very high resolution imaging of structures of biomolecules.  But, to generate an x-ray structure, using this method, the molecule need to be crystallized.  In many cases crystallization alters the original structure. Thus the image may not exactly look like the original structure.  Apart from this, there are many molecules that will not crystallize at all.  The need to study molecules in the native environment led to the invention of Cryo-electron microscopy (cryo-EM). 

What is cryo-electron microscopy (cryo-EM)?

Cryo-electron microscopy, is a form of transmission electron microscopy. Cryo stands for cryogenic. It refers to very low temperature, normally below minus 150°C. In cryo- electron microscopy, the object to be imaged is frozen to very low temperature. The object is then studied by employing the beam of the electron microscope. Cryo-EM is mostly used for researches in structural biology. Cryo-electron microscopy enables observation of specimens in their native environment. 

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Unlike x-ray diffraction, cryo EM can be employed for study of larger proteins, membrane-bound receptors, or complexes of several biomolecules together.   Cryo-electron microscopy helps scientists to overcome the shortfalls of both TEM and x-ray diffraction techniques. 

Who won the Nobel Prize in chemistry in 2017? 

Nobel prize in chemistry in 2017 was awarded to Jacques Dubochet from the University of Lausanne, Switzerland; Joachim Frank from Columbia University, New York, US and Richard Henderson from the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK. They were awarded Nobel prize for the outstanding contributions  ‘for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution’. The scientists are awarded for developing the cryo-electron microscopy that allows researchers to observe the complicated structures of proteins, nucleic acids and other biomolecules, and even their movements. 

Richard Henderson was the first person to develop an image of a protein using TEM. He refined the process over several years and succeeded in generating images with comparable resolutions of  x-ray diffraction. Jacques Dubochet developed a method to  freeze aqueous samples to preserve  shape of molecules. He put ‘cryo’ into cryo-EM. Joachim Frank’s contribution was in processing and analysing cryo-EM images. 

The technology helped researchers in generating a high resolution 3D image of  the Zika virus within three months of its outbreak in Brazil. This enabled identifying suitable drugs to prevent the spread of the virus.

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Cryo-Electron Microscopy: Advanced Version of Microscopy
Article Name
Cryo-Electron Microscopy: Advanced Version of Microscopy
Cryo-Electron Microscopy (cryo EM) is an advanced form of microscopy that allows observation of tiny specimens in their natural environment.

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