Robust coordination of collective oscillatory signaling requires single-cell excitability and fold-change detection [article]

Chuqiao Huyan, Alexander Golden, Xinwen Zhu, Pankaj Mehta, Allyson E. Sgro
2021 bioRxiv   pre-print
Complex multicellular behaviors are coordinated at the level of biochemical signaling networks, yet how this decentralized control mechanism enables robust coordination in variable environments and over many orders of magnitude of spatiotemporal scales remains an open question. A stunning example of these behaviors is found in the microbe Dictyostelium discoideum, which uses the small molecule cyclic AMP (cAMP) to drive the propagation of collective signaling oscillations and spatial waves
more » ... ng to multicellular development. The critical design features of the Dictyostelium signaling network remain unclear despite decades of mathematical modeling and experimental research because the mathematical models make different assumptions about the network architecture. To resolve this discrepancy, we use recent experimental data to normalize the time and response scales of five major signal relay network models to one another and assess their ability to recapitulate experimentally-observed population and single-cell dynamics. We find that to successfully reproduce the full range of observed behaviors, single cells must be excitable and respond to the relative fold-change of environmental signals, suggesting that these features represent robust principles for controlling cellular populations and that single-cell excitable dynamics are a generalizable route for controlling population behaviors.
doi:10.1101/2021.09.02.457527 fatcat:okcwdwhxyfhffbvlwdj5scz7hy