Proving intracellular physiochemical processes at the nanometer scale, one molecule at a time
Recent advances in super-resolution fluorescence microscopy have led to ~10 nm spatial resolution and profound impacts on biology. The obtained structural information, however, does not provide a full picture of how cell functions. We are developing new approaches to advance beyond structural information, and reveal functional information of intracellular physicochemical parameters, including pH, polarity, viscosity, and charge distribution, with nanometer resolution and single-molecule sensitivity. To achieve this goal, we are encoding local environment into the spectral dimension of single-molecule fluorescence, and developing new techniques to synchronously obtain the fluorescence spectra and positions of millions of single probe molecules in live cells. With our initial success with a solvatochromic membrane probe, we revealed nanoscale compositional heterogeneity in the membranes of live mammalian cells and directly visualized polarity differences between the plasma membrane and the membranes of intracellular organelles, as well as raft-like nanoclusters in the plasma membrane. Our endeavor thus offers unprecedented new mechanistic insights into cell behavior and nanoscale (bio)physical chemistry.
Arnold O. Beckman exemplifies the meaning of the word humanitarian. Combined with his unwavering enthusiasm for life, his keen sense of humor and his strong moral and ethical principles, he is a national icon.