Closer to the native architecture of the cell using Cryo-ExM

Most cellular imaging techniques, such as light or electron microscopy, require that the biological sample is first fixed by chemical cross-linking agents. This necessary step is also known to damage molecular nanostructures or even sub-cellular organization. To overcome this problem, another fixation approach was invented more than 40 years ago, which consists in cryo-fixing biological samples, thus allowing to preserve their native state. However, this method has been scarcely used in light microscopy due to the complexity of its implementation. In this review, we present a recently developed super-resolution method called expansion microscopy, which, when coupled with cryo-fixation, allows to visualize at a nanometric resolution the cell architecture as close as possible to its native state.