Adhesive dynamics simulations of sialyl-Lewis(x)/E-selectin-mediated rolling in a cell-free system

Selectin-mediated leukocyte rolling is crucial for the proper function of t he immune response. Recently, selectin-mediated rolling was recreated in a cell-free system (Biophysical Journal 71:2902-2907 (1996)); it was shown th at sialyl Lewis(x) (sLe(x))-coated microspheres roll over E-selectin-coated surfaces under hydrodynamic flow. The cell-free system removes many confou nding cellular features, such as cell deformability and signaling, allowing us to focus on the role of carbohydrate/selectin physical chemistry in med iating rolling. In this paper, we use adhesive dynamics, a computational me thod that allows us to simulate adhesion, to analyze the experimental data produced in the cell-free system. We simulate the effects of shear rate, li gand density, and number of receptors per particle on rolling velocity and compare them with experimental results obtained with the cell-free system. If we assume the population of particles is homogeneous in receptor density , we predict that particle rolling velocity calculated in simulations is mo re sensitive to shear rate than found in experiments. Also, the calculated rolling velocity is more sensitive to the number of receptors on the micros pheres than to the ligand density on the surface, again in contrast to expe riment. We argue that heterogeneity in the distribution of receptors throug hout the particle population causes these discrepancies. We improve the agr eement between experiment and simulation by calculating the average rolling velocity of a population whose receptors follow a normal distribution, sug gesting heterogeneity among particles significantly affects the experimenta l results. Further comparison between theory and experiment yields an estim ate of the reactive compliance of sLe(x)/E-selectin interactions of 0.25 An gstrom, close to that reported in the literature for E-selectin and its nat ural ligand (0.3 Angstrom). We also provide an estimate of the value of the intrinsic association rate (between 10(4) and 10(5) s(-1)) for the formati on of sLe(x)/E-selectin bonds.