Correlative Light Electron Microscopy as a Navigating Tool for Cryo-Electron Tomography Analysis

Modern microscopy techniques, including fluorescence and electron microscopy, have allowed us to gain insights into the molecular organization of cells. Despite the different views attained by fluorescent and electron microscopy, these approaches complement each other in visualizing multicomponent complexes in their native environment. Combining the strengths of both techniques could provide a more realistic view of cellular processes. During the last decade, cryo-electron tomography (cryo-ET) has become central to exploring cellular structures on a nanometric scale. By combining cryo-ET with fluorescence microscopy, it should be possible to localize proteins inside a cell with high precision and by these means to elucidate not only the macromolecular architecture but also the remodeling events during the many cellular processes. Thus, cryo-ET might have the potential to close the resolution gap between cellular and structural biology.