An analysis tool to quantify the efficiency of cell tethering and firm-adhesion in the parallel-plate flow chamber

The parallel-plate flow chamber is applied in immunological studies to quantify the adhesivity of cells (e.g. leukocytes) onto ligand-bearing substrates (e.g. endothelial cells) under fluid-flow conditions that mimic the human vasculature. It is also applied to quantify platelet adhesion in vascular injury models, and tumor cell adhesion in models of cancer metastasis. Typical measures of cell adhesion in this setup include the rolling and adherent cell density. These measures are functions of not only the cellular adhesivity, but also of the physical features of the experimental system (e.g. inlet cell concentration) and observation time. Here, we present a mathematical model to better analyze experimental data on cell rolling, firm-arrest and transmigration. The overall goal is to quantify the biological adhesivity of cells independent of the physical parameters that control the rate of cell-substrate and cell-cell collision. This analysis yields four independent parameters: Primary capture frequency quantifies the rate at which cells in the free stream initiate rolling. Firm-arrest frequency is a measure of the transition from rolling to firm-binding. These two frequency parameters are inversely proportional to the distance the average cell convects in the free stream adjacent to the substrate before tethering, or rolls on the substrate before firm-adhesion, respectively. Rolling-release frequency is introduced to quantify the reversible release of cells from rolling back into the free stream. Finally, cell-cell capture probability quantifies the fraction of collisions between cells in free stream and recruited substrate-bound cells that result in tethering. The proposed analysis methodology may find application in studies of inflammation, thrombosis and cancer research.