Improving the resolution of fluorescence nanoscopy using post-expansion labeling microscopy.

The visualization of the cell ultrastructure and molecular complexes has long been reserved for electron microscopy owing to its nanometric resolution. In recent years, this monopoly has been challenged by super-resolution (SR) fluorescence microscopy, which allows the visualization of cell structures with high spatial resolution, approaching virtually molecular dimensions. However, the resolution of current SR microscopy does not systematically reach the level of the ultrastructural information provided by electron microscopy. In this review, we are discussing the potential of revealing cell ultrastructure using the recent method of expansion microscopy (ExM). In particular, we are discussing the limitations that exist in SR and ExM methods that prevent the visualization of nanometric molecular assemblies and how post-labeling expansion could help alleviate them to reveal the molecular cartography of cells with unprecedented details.