Ke Xu

The living cell creates a complex molecular environment inside its picoliter volume. We discuss our efforts to elucidate molecular environments and interactions in mammalian cells and in vitro through the development of multidimensional single-molecule and super-resolution microscopy. With spectrally resolved single-molecule localization microscopy (SR-SMLM), we unveil nanoscale heterogeneities by encoding functional parameters into the single-molecule emission spectra. With single-molecule displacement/diffusivity mapping (SMdM), we map diffusivity with exceptional spatial resolution and fidelity, thereby uncovering nanoscale diffusion patterns and intermolecular interactions. With SpeedyTrack, we achieve microsecond single-molecule tracking and super-resolution mapping in the wide field, thus pushing single-molecule measurements into new regimes. Together, the integration of multidimensional single-molecule and super-resolution microscopy opens new windows to fascinating molecular patterns and interactions in living cells and beyond.