Statistics of cell adhesion under hydrodynamic flow: simulation and experiment.

Adhesion under hydrodynamic flow is a step in many complicated physiological processes such as the neutrophil-mediated inflammatory response and cancer cell metastasis. We use a combination of computer simulation and experiment to explore how a population of cells interacts with a ligand-coated substrate under shear flow. To simulate the binding of a single cell to a surface, we use a microvilli-hard sphere model in which receptor-ligand bonds are treated as springs, and the net motion of the cell is determined from a force balance involving hydrodynamic, bonding, and colloidal forces. We show that the adhesive phenotype of a cell depends strongly on the fractional spring slippage of receptor-ligand bonds, which relates the extension of a bond to its rate of breakage; a lower spring slippage indicates bonds can withstand a great deal of extension without a significant increase in the breakage rate, and hence leads to more strongly adherent cells. We construct the behavior of a population of cells by simulating many cells using this algorithm. We show that a homogeneous population of cells with identical numbers of receptors, modeled with parameters suitable to recreate neutrophil rolling, will display a distribution of translational velocities. In addition, we calculate the average velocity for a heterogeneous population of cells which has a Gaussian distribution in receptor number. As the standard deviation of this distribution increases, the average observed velocity for the population increases. Although the homogeneous and heterogeneous populations have the same average number of receptors (10(5)) per cell, there is a significant difference in their average velocity when the standard deviation of receptor number in the heterogeneous population is as little as 25% of the average receptor number. We also present experimental evidence that not all cells exhibit the slow rolling characteristic of neutrophil-endothelial interaction, but rather appear to exist in a "binary" state in which cells are either adherent or noninteracting. We have developed an experimental model system for studying adhesion under hydrodynamic flow, using the rat basophilic leukemia (RBL) derivatized polyacrylamide gels in a flow chamber. Cells are injected into a portion of the flow chamber in which the substrate is not coated with antigen, and allowed to flow over the antigen-coated portion of the gel. We have measured the spatial distribution of cell binding for a population of cells at different flow rates, and have shown that cell binding decreases as shear rate increases.(ABSTRACT TRUNCATED AT 400 WORDS)