Identifying key network features coordinating robust collective signaling oscillations

A major challenge in understanding emergent cellular behaviors such as collective oscillations is identifying which features in single-cell signaling networks are essential for robustly coordinating population phenomena. To address this, we focus on one of the most notable examples, the starvation response of the social amoeba Dictyostelium discoideum (Dicty), where cells use collective intracellular cyclic AMP (cAMP) oscillations to mediate a transition from a unicellular to a multicellular state. Taking advantage of recent experimental measurements that a single Dicty cell displays an internal cAMP spike with characteristic height and length in response to an external cAMP input, we were able to normalize the response and time scales of five major models describing group cAMP oscillations in Dicty. This allows us to directly compare models based on how well they reproduce recent experimental data on both single-cell and population behaviors. Our systematic analysis suggests that excitability and fold-change detection are two key features in single-cell signaling networks that coordinate robust population-wide behaviors. This work sheds light on the basic principles in single-cell signaling networks that drive robust population oscillations in biochemically-coupled systems.