Recent advances in the development of new microscopy techniques with a sensitivity of a single molecule have gained access to essentially new types of information obtainable from imaging biomolecular samples. These methodologies are analyzed here in terms of their applicability to the in vivo visualization of cellular processes on the molecular scale, in particular of processes in cell membranes. First examples of single molecule microscopy on cell membranes revealed new basic insight into the lateral organization of the plasma membrane, providing the captivating perspective of an ultra-sensitive methodology as a general tool to study local processes and heterogeneities in living cells.
Methodologies of single molecule microscopy with perspectives of application to living cells discussed in the paper: Single Particle Tracking (SPT), Single Dye Tracing (SDT), Scanning Near-Field Optical Microscopy (SNOM), Atomic Force Microscopy (AFM), Molecular Recognition Force Microscopy (MRFM), Confocal Laser Scanning Microscopy (CLSM), Two-Photon Laser Scanning Microscopy (TPLSM), and Total Internal Reflection Fluorescence Microscopy (TIRFM).