Cryo-TEM and Biological Structure Determination

Cryo‐electron microscopy (cryo‐EM) enables unprecedented insight into the molecular machinery that drives cell life. It involves the study of frozen hydrated samples preserved in a thin layer of vitreous ice, imaged in a transmission electron microscope. The electron radiation used for imaging also damages the samples under study, posing a major limitation on the dose used. The resulting images therefore have very low contrast, requiring that many different 2D views of samples are collected and combined computationally to yield the 3D structures of interest. The field has recently undergone a revolution such that visualisation of a wide range of macromolecular complexes has dramatically improved, including structure determination at atomic resolution. Developments in hardware and software have also increased experimental throughput, making cryo‐EM a central technique in structural and cell biology. The ability of cryo‐EM to bridge biological scales – from atoms to cells – provides an excellent complement to other methods