Nanoscopy of cell architecture: The actin-membrane interface.

It was light microscopy that first revealed the hidden world of bacteria and the unit of life the "cell." From these first observations, made in the late 1600s, it has been clear that seeing is an important tool in biology. The merging of the fields of fluorescence and microscopy created the possibility to see subcellular structures and proteins. In the 1990s the use of the confocal microscopes, where cells/tissue could be optically sectioned, further improved the resolution of object visualization. From this microworld view we now move forward to the exciting prospects of the nanoworld view of biology. In this review I propose a nanoimaging approach, nanoscopy, which could be used to reveal cell architecture at the level of proteins and protein complexes. Nanoscopy includes, the F-techniques, superresolution microscopy, correlative light and electron microscopy and atomic force microscopy. To illustrate the biology that could be investigated by nanoscopy we focus on structures formed at the actin-membrane interface. In particular, focal adhesions and stress fibres have been analyzed using nanoscopy. Many of the proteins present in focal adhesions and stress fibres are shared with structures such as filopodia, lamellipodia, endocytic vesicles, actin pedestals and invadopodia. It is likely that nanoscopy of cells will reveal mechanistic details of biology at the level of individual proteins and protein complexes and importantly in a physiological context.