A cell can be conceived as a factory containing a hierarchical network of nanomachines. Fully understanding the working mechanisms of these nanomachines requires knowledge of both translational and rotational dynamics, and their coupling. The knowledge of rotational dynamics in and on live cells remains highly limited and requires further experimental advances through the use of new innovative tools and new simulations for their interpretation. The Fang Laboratory is one of the leaders in developing optical imaging tools to visualize and understand rotational dynamics in or on living cells. The SPORT technique offers high spatial, angular, and temporal resolutions simultaneously for visualizing rotational motions of anisotropic plasmonic gold nanorods under a differential interference contrast (DIC) microscope. The SPORT technique is capable of extracting important information (including rotational rates, modes, and directions) on the characteristic rotational dynamics in living cells and on cell membranes. It has become possible to acquire first-time live-cell observations on many biological events, such as endocytosis and intracellular transport, and provide a significant new dimensionality to the computational efforts in biology. The new knowledge will lay the groundwork for the development of treatments for conditions caused by the malfunction of the cellular nanomachines, ranging from certain kinds of blindness and kidney disease to neurodegenerative disorders and parasitic diseases, and enable us to create de novo molecular motors for useful, controllable tasks involving mechanical movement at the nanoscopic scale.

An automated calibration and scanning-angle prism-type total internal reflection fluorescence microscopy (TIRFM) has been constructed and tested for vertical resolution of less than 10 nm. This system is being employed for high precision 3D tracking of non-blinking quantum dots, super-resolution imaging of plant cells and tissues, and understanding catalytic reactions on nanocatalysts.