The Motility of Ameboid Cells of the Immune System: Traction Stresses and Directional Motion

Cells of the immune system must traffic throughout the body to identify and eliminate foreign objects, transmit molecular information to other effectors cells, and to maintain immunological homeostasis. The trafficking of immune cells depends on directed cell motility in response to chemokines, where differential occupancy of receptors leads to directed cell motion. Because these cells crawl quickly (several microns/minute), they exert small forces, and measuring traction stresses is a challenge. In this talk, we describe methods to measure the traction stresses during directed cell motility of two critical immune effector cells that are derived from the same progenitor - neutrophils and dendritic cells - under imposition of a gradient of chemokine. For neutrophils, traction measurements were performed using beads embedded in gels, and the traction field was deconvolved from the optical flow (strain field) using two dimensional elasticity theory worked out by Micah Dembo (Boston University). In dendritic cells, we used molecularly stamped polymer micropost arrays, in collaboration with Chris Chen's laboratory at Penn, in which the known elasticity and deflection of the microposts could be used to quantify forces. We found that neutrophils exert squeezing contractile forces in the rear, whereas dendritic cells pull through filopodial extension and contraction in the front. In maximal chemotaxis, the average force exerted by dendritic cells is about a factor of five smaller than that of a neutrophil, and we estimate that a single filopod uses 400 myosin-IIB motors to pull a cell forward. There was a direct correlation between directional motiuon and the magnitude of the root mean squared force required exrted on the substrate. Our spatio-temoral maps of mechanochemical stresses during dendritic cell motility paves the way for detailed modeling of directed cell motion using physiochemical and hydrodynamic models that incorporate contractile and adhesive stresses.