Light microscopy of proteins in their ultrastructural context

Resolving the distribution of specific proteins at the nanoscale in the structural context of the cell is a major challenge in fluorescence microscopy. Here we present a new concept that decrowds the intracellular space through 13 to 21-fold physical expansion while simultaneously retaining the proteins. This combination makes labeling of the proteome efficient enough that local protein densities are revealed and the cellular nanoarchitecture can be visualized by standard light microscopy.