Organic Chemistry Seminar
Rapid changes in membrane potential facilitate the unique physiology of electrically-excitable cells like neurons and cardiomyocytes. Even in non-electrically excitable cells, where membrane potential changes can be much slower, voltage is linked to a variety of cell outcomes including differentiation, cell cycle, and cancer aggressiveness. Despite the central importance of membrane potential dynamics, methods to accurately monitor voltage rely on highly invasive electrodes or indirect optical measurements, such as calcium imaging with fluorescent sensors. Direct visualization of voltage changes has the potential to couple the speed and sensitivity of electrode-based methods with the spatial resolution of imaging approaches. However, the development of fast, sensitive, and bright voltage-sensitive fluorescent indicators remains an outstanding challenge. Here, I present our efforts to design, synthesize, and apply fluorescent indicators that use photoinduced electron transfer (PeT) as a voltage-sensing trigger to achieve fast and sensitive voltage imaging in a variety of biological contexts.