Event-tracking model of adhesion identifies load-bearing bonds in rolling leukocytes.

OBJECTIVES P-selectin binding to P-selectin glycoprotein ligand-1 (PSGL)-1 mediates leukocyte rolling under conditions of inflammation and injury. The aims of this study were to develop an efficient, high temporal resolution model for direct simulation of leukocyte rolling and conduct a study of load-bearing bonds using the model. MATERIALS AND METHODS A stochastic pi-calculus-driven event-tracking model of adhesion (ETMA) was developed and compared with experimental data. Multiple simulations for each case were conducted to obtain high-confidence numerical characteristics of leukocyte rolling. RESULTS Leukocyte rolling and the underlying P-selectin-PSGL-1 bonds were studied under low wall shear rate (25-50 s(-1)) conditions from measured parameters of leukocyte rolling and bond properties. For the first time, the location, number, lifetime, history, and kinetics of load-bearing bonds and their influence on cell rolling were identified and instantaneous cell displacements, translational and rotational velocities, and cell-substrate distances derived. The model explains the commonly observed "stop-start" type rolling behavior and reveals that a few load-bearing bonds are sufficient to support rolling, while a large number of bonds dissociate before becoming load bearing. CONCLUSIONS ETMA provides a method for more precise, direct simulation of leukocyte rolling at low wall shear rates and sets a foundation upon which further refinements can be introduced.