Detecção de mudança de dobra e invariância de escala da sinalização célula-célula na ameba social: mero acaso, fortuita necessidade ou design inteligente???

sexta-feira, maio 12, 2017

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

Keita Kamino a,1, Yohei Kondo a, Akihiko Nakajima b, Mai Honda-Kitahara a, Kunihiko Kaneko a,b, and Satoshi Sawai a,b,c,1 

Author Affiliations

a Department of Basic Science, Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153-8902, Japan;

b Research Center for Complex Systems Biology, University of Tokyo, Tokyo 153-8902, Japan;

c Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan

Edited by Peter N. Devreotes, The Johns Hopkins University School of Medicine, Baltimore, MD, and approved April 9, 2017 (received for review February 9, 2017)


Recent works have hinted at an ability of cells to respond in the exact same manner to a fold change in the input stimulus. The property is thought to allow cells to function properly regardless of changes in the absolute concentrations of signaling molecules. Despite its general importance, however, evidence has remained scarce. The present work demonstrated that, in the social amoeba Dictyostelium, a response to cell–cell communication molecules is fold-change dependent and that this property is tightly linked to the condition that allows them to oscillate collectively, and thus to organize into a multicellular form. Such properties may be of importance for robustness of other developmental systems where oscillatory signaling plays a pivotal role in defining multicellular organization.


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.

fold-change detection oscillations collective behavior Dictyostelium robustness


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Author contributions: K. Kamino, Y.K., K. Kaneko, and S.S. designed research; K. Kamino, Y.K., A.N., and S.S. performed research; M.H.-K. and S.S. contributed new reagents; K. Kamino and A.N. acquired and analyzed live cell image data; K. Kamino and Y.K. performed theoretical and computational analysis; and K. Kamino, Y.K., and S.S. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

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Freely available online through the PNAS open access option.