A measure of molecular muscle: Development and application of fluorescence-based probes to map piconewton forces in living systems

A major challenge to understanding the role of forces in cell biology pertains to the lack of molecular tools that allow one to image and manipulate forces at the piconewton scale (1 kcal/mol ~7pN*nm). To address this issue, we have developed a suite of fluorescent tension probes. Tension probes are modular and can be engineered using PEG polymers, oligonucleotides, and proteins. The latest generation of tension probes employ plasmonic nanoparticles, which provides significant improvement in sensitivity. Fluorescence polarization spectroscopy and super-resolution imaging provide the highest resolution maps of cell forces. I will also describe the application of these probes in the study of integrin and T cell receptor mechanobiology. Finally, I will also demonstrate mechano-pharmacology applications of our force probes.