Estimation of cell capture and arrest efficiency in flow chambers

Abstract

The parallel-plate flow chamber has been widely applied to study the biophysics of receptor-ligand interactions under physiologically relevant hydrodynamic flow conditions. We developed a mathematical model to quantify cell-substrate attachment efficiency in the parallel-plate flow chamber. Different frequency parameters are introduced to quantify the efficiency with which cells in the flow chamber: i) progress from the free stream to rolling, ii) switch from rolling to firm arrest, and iii) release from either rolling or firm arrest back into the free stream. Cell-cell capture probability is also introduced to distinguish between cell-substrate binding events (primary capture) and cell-cell binding (secondary capture). Thus the model decouples the physical features of the system that affect the rate of cell-substrate collision from the biological features that influence its adhesivity. It is partially validated by comparing simulation results with experimental data where neutrophils rolled and adhered onto substrates composed of cotransfected cells bearing E-selectin and InterCellular Adhesion Molecule-1 (ICAM-1). We also estimated the lumped on-rate for selectin-ligand interactions in both the cellular systems with the cotransfected cells and in reconstituted systems with immobilized soluble E-selectin. The on-rates estimated in both systems compared favorably. The on-rates of selectins vary as: L-selectin>P-selectin>E-selectin.