This project will examine to what extent cell-cell interactions affect the accumulation of neutrophilis at a site of inflammation. Flow chamber experiments with both ligand-coated hard spheres and neutrophilis show that selectin-mediated leukocyte rolling is inherently noisy, with intermittent pauses in motion. These pauses allow integrin bonds to form, firmly adhering a rolling cell for subsequent extravasation. We hypothesize that cell collisions and concentrated suspension rheology influence the dynamics of rolling, and thus, the transition to firm arrest. To test this hypothesis a novel calculational technique will be used to directly simulate cell adhesion in a multi-cell system. The hydrodynamics of cellular interactions in the fluid will be rigorously calculated using the Stokesian Dynamics method, combined with a quantitative model of the chemical interactions between cell and substrate. The resulting theoretical predictions will be tested with flow chamber experiments using a higher concentration of cells or coated beads than has been previously studied. This study is intended to bridge the gap between in vitro and vivo observations of leukocyte rolling, specifically, that rolling behavior is supported at much higher shear stresses in vivo.
| King, M R; Hammer, D A (2001) Multiparticle adhesive dynamics. Interactions between stably rolling cells. Biophys J 81:799-813 |
