Multiparticle adhesive dynamics: Hydrodynamic recruitment of rolling leukocytes

Abstract

The slow rolling motion of leukocytes along the walls of blood vessels mediated by specific receptor-ligand adhesion is important in inflammation and occurs in postcapillary venules over a wide range of wall shear stresses and vessel diameters. The ability of hydrodynamic collisions between cells to induce capture of freestream leukocytes to a selectin-bearing surface under shear flow was studied experimentally by using a cell-free assay. It was found that carbohydrate-coated spherical beads, representing model leukocytes, tend to attach to the adhesive wall 4 -5 cell diameters up-or downstream of a slowly rolling or stationary adhesive bead. A key feature of such ''hydrodynamic recruitment'' is that only glancing, indirect collisions occurring close to the plane will result in downstream attachment. A direct numerical simulation of cell capture and rolling that includes multiparticle hydrodynamic interactions is shown to reproduce the observed behavior accurately. The theory predicts that hydrodynamic recruitment will occur in the absence of buoyancy effects and over a range of shear rates, suggesting that the mechanism may be important in vivo. This theory is supported by measurements of leukocyte capture in vivo using the hamster cheek pouch model. The adhesion of cells with surfaces in the microvasculature is important in the inflammatory response (1), lymphocyte homing to lymphatic tissues, and stem cell homing (2). A key step in these adhesive interactions is rolling, in which the adhesion of cells to surfaces slows but does not stop the motion of a cell under hydrodynamic flow. Rolling is caused by the coordinated formation and breakage of receptor-ligand bonds at the front and back of the cell, respectively. Initial adhesive contact in inflammation is mediated by the selectin family of molecules: P-and E-selectin, expressed on the surface of endothelial cells, and L-selectin, which is found at the tips of leukocyte microvilli and their corresponding ligands (3). Rolling leads to firm adhesion and the accumulation of neutrophils at inflammatory sites, the binding of monocytes to atherosclerotic sites (4), and the homing of stem cells to bone marrow (5). Because these physiological phenomena require the accumulation of many cells, a quantitative model of the factors that lead to cell accumulation is needed.The experimental basis for leukocyte accumulation in vivo has a long history. Addison (6) first observed that 0.5 h after the application of a crystal of salt to the web of a frog's foot, the number of adherent white cells increased considerably and resulted in complete ''pavementing'' of the vessel wall overnight. Intradermal injection of foreign substances was found to result in leukocyte accumulation near the region of injury in rabbit ear (7) and rat skin (8). Kopaniak et al. (9) quantified the accumulation of neutrophils at the site of intradermal injection of killed Escherichia coli, showing a peak of 7,000 cells per site after 2.5 h and a decrease to zero adhesion after 6 h. Leukocyte accumulatio...

P-Selectin–Coated Microtube for Enrichment of CD34+ Hematopoietic Stem and Progenitor Cells from Human Bone Marrow

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Quantifying the biophysical characteristics of Plasmodium-falciparum -parasitized red blood cells in microcirculation

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Catch Strip Assay for the Relative Assessment of Two-Dimensional Protein Association Kinetics

“…field 7 or collisions between microparticles 8 may have an impact on accumulation on the surface. Finally, depending on the immobilization technique employed, the adhesive ligand may not be evenly distributed on the surface.…”