From Microscope to Model: Rotating Signaling Dynamics and Cluster Size in Dictyostelium Discoideum Aggregates.

When starved, Dictyostelium Discoideum cells form aggregates that, when constrained in height, exhibit collective rotational motion. To maintain this collective rotation, cells secrete and relay the chemoattractant cAMP, resulting in signal propagation in the form of spiral waves which rotate in the opposite direction of the collective rotation. The quantification of this collective rotation with reference to cAMP signaling and the dependence on cluster size are currently unclear. In this study, we use both experiments and simulations to investigate how cell motion and cAMP signaling dynamics depend on aggregate sizes in Dictyostelium aggregates. We show agreement between experimental and simulation data using the 2D Cellular Potts model coupled with the reaction diffusion equation for cell excitability. For rotating clusters with a single spiral arm, our findings indicate that both wave and cell rotation speeds decrease as cluster size increases, suggesting that larger clusters signal more slowly. We also show that cell rotation speed increases linearly with wave rotation speed. For clusters with multiple spiral arms, we observe a size dependence where larger clusters have a higher probability of having more spiral arms compared to smaller clusters. While our findings suggest that aggregate size influences the signaling properties of cell clusters at the microscopic level, more studies are required to establish the feedback between cluster-scale and microscopic properties.