Physical Society Colloquium

Forces and mechanosensing in immune cells

Arpita Upadhyaya

Department of Physics
University of Maryland

Cells need to sense and adaptively respond to their physical environment in diverse biological contexts such as development, cancer and the immune response. In addition to chemical signals and the genetic blueprint, cellular function and dynamics are modulated by the physical properties of their environment such as stiffness and topography. In order to probe and respond to these environmental attributes, cells exert forces on their surroundings and generate appropriate biochemical and genetic responses. These forces arise from the spatiotemporal organization and dynamics of the cell cytoskeleton, a network of entangled biopolymer filaments that is driven out of thermal equilibrium by enzymes that actively convert chemical energy to mechanical energy. Understanding how cells generate forces and sense the mechanical environment (mechanosensing) is an important challenge with implications for physics and biology. We have investigated the principles of cellular force generation, the statistical properties of these forces, and their role in stiffness and topography sensing by immune and cancer cells. During activation, immune cells interact with structures possessing a diverse range of physical properties and respond to physical cues such as stiffness, topography and ligand mobility. We have used traction force microscopy to measure the forces exerted by T cells during activation on elastic substrates. I will discuss the distinct roles of the actin and microtubule cytoskeleton in the exertion of mechanical stresses that support signaling activation, microcluster assembly and receptor movement in T cells. We found two spatially distinct regimes of force generation, potentially arising from different actin-based structures. Furthermore, T cells are mechanosensitive, as cytoskeletal dynamics, force generation and signaling are modulated by substrate stiffness. Our recent studies have also shown that actin dynamics and signaling in B cells is modulated by subcellular topography of the antigen-presenting surface. Our work highlights the importance of cytoskeletal forces in immune cell receptor activation.