Advances in Cryo-Correlative Light and Electron Microscopy: Applications for Studying Molecular and Cellular Events

Cryo-correlative light and electron microscopy (Cryo-CLEM) is materializing as a widespread approach amalgamating the advantages of both fluorescence light microscopy (FLM) as well as three dimensional (3D) cryo-electron tomography (cryo-ET) to reveal the ultrastructure of significant target molecules with specific cellular functions. Cryo-CLEM allows imaging of cells by means of fluorescence microscopy exhibiting the location of the destined molecule at high temporal and spatial resolution while cryo-ET is employed to analyze the 3D structure at a molecular resolution in close-to-physiological condition. Present review focuses upon the practical strategies for Cryo-CLEM and recent technical developments that will assist the broad implementation of this technique to investigate and answer questions pertaining to various biological events occurring in the cell.