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Proc Natl Acad Sci U S A. 2017 May 23;114(21):E4149-E4157. doi: 10.1073/pnas.1702181114. Epub 2017 May 11.

Fold-change detection and scale invariance of cell-cell signaling in social amoeba.

Author information

Department of Basic Science, Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153-8902, Japan;
Department of Basic Science, Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153-8902, Japan.
Research Center for Complex Systems Biology, University of Tokyo, Tokyo 153-8902, Japan.
Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.


Cell-cell signaling is subject to variability in the extracellular volume, cell number, and dilution that potentially increase uncertainty in the absolute concentrations of the extracellular signaling molecules. To direct cell aggregation, the social amoebae Dictyostelium discoideum collectively give rise to oscillations and waves of cyclic adenosine 3',5'-monophosphate (cAMP) under a wide range of cell density. To date, the systems-level mechanism underlying the robustness is unclear. By using quantitative live-cell imaging, here we show that the magnitude of the cAMP relay response of individual cells is determined by fold change in the extracellular cAMP concentrations. The range of cell density and exogenous cAMP concentrations that support oscillations at the population level agrees well with conditions that support a large fold-change-dependent response at the single-cell level. Mathematical analysis suggests that invariance of the oscillations to density transformation is a natural outcome of combining secrete-and-sense systems with a fold-change detection mechanism.


Dictyostelium; collective behavior; fold-change detection; oscillations; robustness

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