ABSTRACT: Immune cells interact with complex environments through receptors to gather information and defend against infections and cancer. For example, in the adaptive immune system, T cells leverage mechanical forces through their T cell receptors (TCRs) during antigen recognition to make biochemical decisions, such as killing infected or cancerous cells. How do we investigate these mechanical interactions generated by cells, as well as their significance in immune signaling? In this talk, I will introduce DNA-based tension probes—molecular tools that capture the magnitude and kinetics of receptor forces in live cells. We use these probes to map the dynamic forces exerted by TCRs during antigen recognition, revealing receptor force magnitude and kinetic signatures that correlate with immune activation. Beyond TCRs in the adaptive immune system, we turn to the innate immune system, where natural killer (NK) cells initiate killing through antibody-dependent cellular cytotoxicity (ADCC), a process whose mechanical cues remain unexplored. We uncovered that NK cells transmit defined
piconewton-scale receptor forces during activation, which are associated with cytoskeletal activity and cell signaling. Decoding these “forces of habit” in adaptive and innate immune cells provides a biophysical understanding of fundamental immune processes and insights for advancing cancer immunotherapy strategies.

BIOSKETCH: Dr. Rong Ma is a postdoctoral fellow working at the intersection of mechanobiology, DNA nanotechnology, and immunology. She earned her PhD from Emory University in 2021, where she focused on developing DNA-based molecular tools to investigate physical forces generated by cells through receptor-ligand interactions, specifically via T cell receptors and integrins. She then received the Michelson Prize: Next Generation Grants, and was selected as a Stanford Science Fellow in 2022. At Stanford, she focuses on conducting independent research on mechanical signaling during natural killer cell activation. Her interdisciplinary research bridges molecular and cellular engineering with cellular biophysics, offering insights into how tiny mechanical forces can profoundly influence immune responses, as well as inspiration for novel immunotherapeutic design.