Cryo Electron Microscopy and Electron tomography

High resolution molecular cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET) represent unique tools in cell biology to understand the relationship between structure and function. These techniques are powerful and perfectly suited techniques for the study of large and complex molecular machines in their dynamic forms as well as for the study of complex cellular events (such as membrane fusion, cell division, protein trafficking, DNA replication, translation…). These techniques have been successfully applied to resolve the structure of dynamic large protein complexes that are difficult to study with other structural techniques such as X-ray crystallography and NMR.

These cryogenic techniques allow the visualization of fully hydrated samples that are observed in the transmission electron microscope (TEM). Samples are rapidly frozen to avoid damage caused by ice crystal formation and the ultrastructure is well preserved without staining or drying artifacts.

Recent technical advances have given the impetus to cryo-EM and cryo-ET. None-the-less, the number of protein complexes that have been studied using cryo-EM and cryo-ET is still infinitesimal compared to the number of protein complexes that form in the cell, which are being discovered using biochemistry and proteamic techniques. These techniques are thereby in full extension.