Chemical Approaches to Visualize and Quantify Cellular Physiology

The importance of membrane potentials is most widely recognized in electrically excitable cells in organs like the brain, the heart, and muscles. However, all cells maintain a membrane potential. Small differences in these electric fields have been linked to enhanced cell signaling, differentiation, development, control of circadian rhythms, modulation of ultradian rhythms, regulation of cell volume, proliferation, cell cycle progression, metastatic potential of cancerous tumors, and more. Across all cell types, up to 50% of the cellular ATP budget is spent on setting the membrane potential via the action of the ATP-powered Na+/K+ exchanger. Despite the massively expensive energy expenditure put out by cells to maintain this electrical potential, a clear picture of the details of how bioelectrical signals and potentials shape physiology outside of the brain remains elusive. The lack of readily implemented methods to reliably measure membrane potential values has limited progress in the field of understanding how bioelectrical signals shape cellular physiology outside of the context of the brain. A vast ecosystem of electrical signals outside of the brain exists between and within cells. This interconnected network has been previously inaccessible. Electrodes fall short when measuring multiple cells or accessing intracellular membranes. Existing dyes are prone to serious artifacts that confound a straightforward interpretation. We are developing optical methods to address these existing shortcomings and visualize and quantify bioelectrical signals and potentials in cells and in organelles outside of the context of the brain. We combine approaches and methodologies from synthetic chemistry, physiology, and cell biology to make contributions to understand the chemistry of fluorophores for live cell imaging, uncover new vistas of cellular physiology across cells and within cells, and take translational approaches with implications for understanding drug-ion channel interactions.