MRC National Institute for Medical Research, London
Science for Health
Cryo electron microscopy
High resolution Cryo Electron Microscopy (CryoEM) enables the structure of biological molecules and larger materials to be visualised in a frozen hydrated state without fixation or staining.
An aqueous solution containing the specimen is frozen very rapidly to liquid nitrogen temperatures. When cooled rapidly, water turns to a glass (rather than forming ice crystals) and the embedded biological material, locked in this transparent medium, can be viewed by electron microscopy. Because the electron beam has a much shorter wavelength than visible light, individual protein molecules can be visualised. Although the image contrast of each individual molecule is low, signal averaging can reveal near-atomic resolution structural information.
CryoEM is well-suited to highresolution studies of both the structure and dynamics of large proteins and protein complexes (e.g. cytoskeletal proteins or viral capsids). Our latest methods also enable structures within rapidly frozen mammalian cells to be visualised. By recording many digital images of a specimen held at different orientations (tomography), a three-dimensional view of the molecule or cell is obtained. Individual molecules, whole virus particles or living mammalian cells, embedded in ice can be imaged in three-dimensions.
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Slice of a three-dimensional tomogram showing the edge of a frozen-hydrated cell and a computational model for membrane organelles (Image courtesy of Sebastian Wasilewski).
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