Invited Talk

Feeling the force: molecular tools for quantifying cellular traction forces

Emory University, Dept. of Chemistry, Atwood Hall, 1515 Dickey Drive Atlanta, GA 30322, USA

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Cells are highly dynamic structures that are constantly converting chemical energy into mechanical work to pull and push on one another and on their surroundings. These pulls and pushes are mediated by tiny molecular forces at the scale of tens of piconewtons. For context, 7 pN applied a distance of 1 nm is ~1 kcal/mol. Nonetheless, these forces can have profound biochemical consequences. For example, the rapidly fluctuating forces between immune cells and their targets can drastically tune immune response and function. Despite the importance of mechanics there are limited methods to study forces at the molecular scale and particularly within the context of living cells. In this talk, I will discuss my group’s efforts at addressing this gap in knowledge by developing tools to measure and map the molecular forces applied by cells. I will describe the development of a suite of molecular DNA tension probes. DNA tension probes offer significant improvements in signal/noise and also lead to enhanced spatial and temporal resolution. I will also describe a series of force-triggered reactions that enable signal amplification and tagging of cells. Fluorescence polarization spectroscopy and super-resolution imaging offer the highest resolution maps of cell traction forces reported to date. I will also describe the application of these probes in the study of cell adhesions, podosome formation, and T cell receptor mechanobiology. Finally, armed with these new tools, I will describe the advent of translational mechanobiology where we apply force sensors toward predicting cell behavior.