Fig. 4. Proposed model for local directional decision making in human neutrophils interacting with posts.

(a) Dynamics of the cytoskeleton during the interaction with the posts. (b) Simulated trajectory of successful (blue) and failing (red) leading edges containing six dynamic microtubules with a characteristic Poisson timescale of 40 s. During the time shown, the successful leading edge (blue) remains intact since it undergoes random microtubule collapses at well separated times of t = 33 s, 53 s and 61 s, respectively. In contrast, the failing leading edge (red) undergoes random microtubule collapses at closely spaced time intervals, starting at t = 39 s, with subsequent failures every 4 s or less. This causes sudden and large increases in load on the remaining microtubules that trigger their subsequent collapse. At t=61 s, the total catastrophic failure of all microtubules causes the leading edge to begin retracting. In the inset, five simulated trajectories are shown that were generated using these same parameters. (c) A comparison between simulated and observed extension time of the two leading edges, during the interaction between neutrophils and posts, shows good qualitative and quantitative agreement between the two. The stochastic behavior and the highly asymmetric distribution are relatively insensitive to the choice of parameters. Parameters were selected to match the experiments, particularly the median timescale of 60 s.