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 the immune response. Recently, selectin-mediated rolling was recreated in a cell-free system (Biophysical Journal 71:2902-2907 (1996)); it was shown that sialyl Lewis(x) (sLe(x))-coated microspheres roll over E-selectin-coated surfaces under hydrodynamic flow. The cell-free system removes many confounding cellular features, such as cell deformability and signaling, allowing us to focus on the role of carbohydrate/selectin physical chemistry in mediating rolling. In this paper, we use adhesive dynamics, a computational method that allows us to simulate adhesion, to analyze the experimental data produced in the cell-free system. We simulate the effects of shear rate, ligand 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 more sensitive to shear rate than found in experiments. Also, the calculated rolling velocity is more sensitive to the number of receptors on the microspheres than to the ligand density on the surface, again in contrast to experiment. We argue that heterogeneity in the distribution of receptors throughout the particle population causes these discrepancies. We improve the agreement between experiment and simulation by calculating the average rolling velocity of a population whose receptors follow a normal distribution, suggesting heterogeneity among particles significantly affects the experimental results. Further comparison between theory and experiment yields an estimate of the reactive compliance of sLe(x)/E-selectin interactions of 0.25 A, close to that reported in the literature for E-selectin and its natural ligand (0.3 A). We also provide an estimate of the value of the intrinsic association rate (between 10(4) and 10(5) s(-1)) for the formation of sLe(x)/E-selectin bonds.
Chang
K C
KC
School of Chemical Engineering, Cornell University, Ithaca, New York 14853 USA.
Hammer
D A
DA
D055592:Biophysical Phenomena; D001703:Biophysics; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D002474:Cell-Free System; D019040:E-Selectin / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000502:physiology; D008863:Microspheres; D008954:Models, Biological; D009844:Oligosaccharides / Q000502:physiology*; D000080506:Sialyl Lewis X Antigen
D019040:E-Selectin; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen