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Cytoskeletal Architecture and Macromolecular Structure in Intact Eukaryotic Cells Revealed by Cryo-Electron Tomography

It has been a long-term ambition of cell biologists to catch a glimpse of the molecular architecture inside cells or organelles, ideally by a non-invasive technique 1 . With the advant of automated electron tomography 2,3 it has becomes possible to obtain tomographic data sets of frozen hydrated specimen at sub-critical electron doses. Electron tomography is currently the only technique that can retrieve 3-D information from large pleomorphous structures 4 , as cell organelles or whole cells with ‘molecular resolution’. Currently the resolution obtained with ice-embedded cellular structure is in the range of 4 to 6 nm, but there is room for improvement; 2 to 4 nm are within reach. At that resolution it becomes possible to detect and identify specific macromolecular complexes on the basis of their structural signature 5 .