Three-Dimensional Computational Modeling of Leukocyte Rolling and Adhesion

Recruitment of leukocytes into sites of acute and chronic inflammation is a vital component of the innate immune response in humans and plays an important role in cardiovascular diseases, such as ischemia-reperfusion injury and atherosclerosis. Leukocytes extravasate into the inflamed tissue through a multi-step process, which involves initial contact of a leukocyte with activated endothelium (tethering or capture), leukocyte rolling, firm adhesion, and transendothelial migration. We developed a computational fluid dynamics algorithm for fully three-dimensional transient simulations of multiphase viscoelastic problems. The algorithm was applied to model leukocyte rolling and adhesion in a parallel-plate flow chamber. In the model, the leukocyte is a viscoelastic cell with the nucleus located in the intracellular space and cylindrical microvilli distributed over the cell membrane. Leukocyte-endothelial cell interactions are mediated by cell adhesion molecules expressed on the tips of leukocyte microvilli and on endothelium. We show that the model can predict both shape changes and velocities of rolling leukocytes under physiological flow conditions. Results of this study indicate that viscosity of the cytoplasm is a critical parameter of leukocyte adhesion, affecting the cell’s ability to roll on endothelium.