Journal
BIOLOGY OF THE CELL
Volume 108, Issue 9, Pages 245-258Publisher
WILEY
DOI: 10.1111/boc.201600008
Keywords
Cryo-CLEM; Cryo-imaging; Nanoscopy; SRM; TEM
Categories
Funding
- Wellcome Trust [107806/Z/15/Z, 090532/Z/09/Z, 107457/Z/15/Z]
- Human Frontiers grant [RGP0055/2015]
- Wellcome Trust [107806/Z/15/Z] Funding Source: Wellcome Trust
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Correlative light and electron microscopy (CLEM) has become a powerful tool in life sciences. Particularly cryo-CLEM, the combination of fluorescence cryo-microscopy (cryo-FM) permitting for non-invasive specific multi-colour labelling, with electron cryo-microscopy (cryo-EM) providing the undisturbed structural context at a resolution down to the angstrom ngstrom range, has enabled a broad range of new biological applications. Imaging rare structures or events in crowded environments, such as inside a cell, requires specific fluorescence-based information for guiding cryo-EM data acquisition and/or to verify the identity of the structure of interest. Furthermore, cryo-CLEM can provide information about the arrangement of specific proteins in the wider structural context of their native nano-environment. However, a major obstacle of cryo-CLEM currently hindering many biological applications is the large resolution gap between cryo-FM (typically in the range of approximate to 400 nm) and cryo-EM (single nanometre to the angstrom ngstrom range). Very recently, first proof of concept experiments demonstrated the feasibility of super-resolution cryo-FM imaging and the correlation with cryo-EM. This opened the door towards super-resolution cryo-CLEM, and thus towards direct correlation of structural details from both imaging modalities.
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