Estimating the efficiency of cell capture and arrest in flow chambers: study of neutrophil binding via E-selectin and ICAM-1

ABSTRACT A mathematical model was developed to quantify the efficiency of cell–substrate attachment in the parallel-plate flow chamber. The model decouples the physical features of the system that affect cell–substrate collision rates from the biological features that influence cellular adhesivity. Thus, experimental data on cell rolling and adhesion density are converted into “frequency ” parameters that quantify the “efficiency ” with which cells in the flow chamber progress from the free stream to rolling, and transition from rolling to firm arrest. The model was partially validated by comparing simulation results with experiments where neutrophils rolled and adhered onto substrates composed of cotransfected cells bearing E-selectin and intercellular adhesion molecule-1 (ICAM-1). Results suggest that: 1) Neutro-phils contact the E-selectin substrate on average for 4 – 8.5s before tethering. This contact duration is insensitive to applied shear stress. 2) At 2 dyn/cm2, 28 % of the collisions between the cells and substrate result in primary capture. Also, 5–7 % of collisions between neutrophils in the free stream and previously recruited neutrophils bound on the substrate result in secondary capture. These percentages were higher at lower shears. 3) An adherent cell may influence the flow streams in its vicinity up to a distance of 2.5 cell diameters away. 4) Our estimates of selectin on-rate in cellular systems compare favorably with data from reconstituted systems with immobilized soluble E-selectin. In magnitude, the observed on-rates occur in the order, L-selectin P-selectin E-selectin. GLOSSARY Note: All vector quantities are in bold. Variables with asterisk in superscript are in dimensionless form. uym value of the variable u at position y m. a, ae cell radius, radius of receptor–ligand encounter complex A, A-1, Atot adhesion flux, adhesion release flux, total adherent cell density b half chamber height C, Cb cell concentration per unit volume at any point, at the inlet of the flow chamber Cr rolling cell concentration per unit area CL ligand concentration per unit substrate are