Figure 2

Sketches of in vitro and in silico experimental system components. (A) A LEUKOCYTE object is shown pulled away from the simulated flow chamber surface to which it was attached. The left arrow indicates ROLL direction; the three right arrows indicate SHEAR resulting from the simulated flow. The simulated flow chamber surface is discretized into independent units of function called SURFACE UNITS. The LEUKOCYTE'S MEMBRANE is similarly discretized into matching units of function called MEMBRANE UNITS: 600 total (20 × 30). The 8 × 10-shaded region on the SURFACE and on the underside of the LEUKOCYTE identifies the CONTACT ZONE. The UNITS within the CONTACT ZONES that are shaded differently indicate different numbers of BONDS had formed between LIGAND-LIGAND pairs in overlapping UNITS; otherwise, no BONDS formed. ROLLING is the result of a sequence of forward ratchet events. One ratchet event is the result of one row of MEMBRANE UNITS being released at the rear of the CONTACT ZONE along with engagement of a new row of at the front of the CONTACT ZONE. One ratchet event maps to a leukocyte rolling 1 μm (relative to the flow chamber surface). (B) A shop drawing of a typical parallel plate flow chamber used for in vitro studies of leukocyte rolling and adhesion. A video microscope is used to record leukocyte behaviors. (C) MEMBRANE UNITS are illustrated. Each MEMBRANE UNIT is simulated using a software object functioning as a container. In this sketch, nine MEMBRANE UNIT containers are shown. All leukocyte membrane functionality (relevant to these studies) within each UNIT is represented by three objects functioning as agents: PSGL1, VLA4 and CXCR2 (illustrated as spheres). The number of leukocyte ligands being represented by each is typically different from UNIT to UNIT, as illustrated by the numbers on the spheres. That number is specified for each simulation using parameter values from Table 3.