(470a) 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.