Figure 1.
Overview of single-cell/single-target experiment and computer model.
(A) Example videomicrographs of a phagocytosis experiment showing the typical initial response of a pipette-held neutrophil to adhesive contact with a zymosan particle. The dashed line depicts part of the time-dependent positional trajectory of the target center (measured relative to the opposite edge of the main cell body, red line). The scale bar is 10 µm. (B) Snapshot of a computer simulation. The zymosan particle is modeled as a rigid sphere. The insets enlarge the pseudopod engulfing the particle. The leading, white membrane patch marks the region where a signaling messenger is produced. The coloring of the lamella interior reflects the relative density of the cytoskeletal actin network (top half) and the relative concentration of the messenger (bottom half).
Figure 2.
Comparison of optimal computer simulations with experimental observations.
(A and F) Filmstrips of videomicrographs of neutrophil phagocytosis of a zymosan particle (A) and an antibody-coated bead (F). The scale bar is 10 µm. (B and E) Snapshots of our simulations of the engulfment of zymosan (B) and antibody-coated targets (E). Note that the simulations were optimized to reproduce the average experimental behavior and are not the best match to the examples in (A) and (F). The coloring of the cell interior reflects the relative density of the cytoskeletal actin network. (C and D) Comparison of time-course graphs of three typical experimental target trajectories (noisy dark-gray curves, cf. Fig. 1A) with the respective results of the optimal simulations (red) for both forms of phagocytosis. Also shown are measured (light-gray curves) as well as prescribed, simplified cortical tension timelines (blue).
Table 1.
Summary of mechanoeffectors in the target-specific computer models.
Figure 3.
Elimination of potential mechanisms of zymosan phagocytosis due to mismatch between the predictions of the respective computer simulations and experimental results.
The noisy, light-gray curve is a “benchmark” positional trace of a zymosan particle as typically measured in single-cell experiments. Trajectories of unsuccessful simulations are shown in blue (original Fcγ model without attractive force) and red (after adding a full-strength protrusive force at the cell-target contact region). Included are snapshots of unsatisfactory simulations corresponding to the time points marked by circles.