From microscope to model: rotating signaling dynamics and cluster size in Dictyostelium discoideum aggregates.

backgroundWhen starved, Dictyostelium discoideum cells form clusters that, when constrained in height, exhibit clear collective rotational motion. During 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 is currently unclear.

resultsIn this study, we use experiments and modeling to investigate how cell motion and cAMP signaling dynamics depend on cluster sizes in Dictyostelium using aggregates that are confined to quasi-2D environments. For rotating clusters with a single cAMP spiral arm, we find that both cAMP wave and cell angular velocities decrease as cluster sizes increase, suggesting that larger clusters signal more slowly. We also show that the angular velocity of the cells ([Formula: see text]) is linearly correlated with the angular velocity of the cAMP wave ([Formula: see text]). 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. The qualitative experimental results are consistent with a computational model that couples a reaction diffusion model to cell motility and chemotaxis. Our simulation results suggest that a variable degradation rate of cAMP, which depends on cluster size, is a possible mechanism to explain the cluster size-dependent wave and cell angular velocities.

conclusionTogether, these findings identify cluster size as a key regulator of both cAMP wave dynamics and collective cell motion and link slower signaling and enhanced multi-armed spiral formation to larger clusters. More broadly, our work suggests that size-dependent modulation of extracellular cAMP degradation can couple cell number to emergent spatiotemporal patterns in developing Dictyostelium aggregates.