Fig. 3
Change of the wave dynamics on the mesoscale heterogeneity. (a–c) Pulse-count for 4,233 cells in a 2.2 × 2.2 mm2 area at the time when cluster-1 experienced the 8th (a), 12th (b), and 13th wave propagation (c), while Clusters-2–4 experienced fewer rounds of wave propagation. Cells with a higher pulse-count are shown in a warmer color, whereas non-pulsing cells are shown as gray dots. For better visibility, cells with pulse-counts of 1 and 0 are shown as small dots. The gray lines in (a) outline the cluster of highly pulsed cells at 8th wave propagation. To show the spatial expansion of clusters, the same outlines as in (a) are shown in (b) and (c), so that the newly pulsing cells outside the cluster outlines in (b) and (c) indicate cluster development. (d–f) cAMP waves at the 8th (d), 12th (e), and 13th wave propagation (f) represented by interaction links (arrows) between cells with pulse-counts larger than 0 (gray dots). The arrow indicates the direction of cAMP relaying. The temporal flow of cAMP pulsing from cluster-1 (see (g)) is shown with color-coded arrows, while the others are shown with gray arrows. (g–i) Schematic representations of the cAMP wave at the 8th (g), 12th (h), and 13th propagations (i). The wave dynamics changed from intracluster (g) to intercluster propagation (h,i). For simplicity, the morphologies of the clusters at eighth wave propagation are shown in (h) and (i). The asterisk in (i) indicates the wave-impermissive pocket. (+) indicates the wave initiation position. Green and magenta represent the wavefront and wave propagation direction, respectively. Mesh size for analysis regions of interest (ROIs), 110 μm.
