Abstract

Collective behavior in cellular populations is coordinated by biochemical signaling networks within individual cells. Connecting the dynamics of these intracellular networks to the population phenomena they control poses a considerable challenge because of network complexity and our limited knowledge of kinetic parameters. However, from physical systems, we know that behavioral changes in the individual constituents of a collectively behaving system occur in a limited number of well-defined classes, and these can be described using simple models. Here, we apply such an approach to the emergence of collective oscillations in cellular populations of the social amoeba Dictyostelium discoideum. Through direct tests of our model with quantitative in vivo measurements of single-cell and population signaling dynamics, we show how a simple model can effectively describe a complex molecular signaling network at multiple size and temporal scales. The model predicts novel noise-driven single-cell and population-level signaling phenomena that we then experimentally observe. Our results suggest that like physical systems, collective behavior in biology may be universal and described using simple mathematical models.

Highlights

  • Collective behavior is a common feature of many biological systems and is present in systems ranging from flocking birds, human spectators, schooling fish, and circadian rhythms in many higher organisms, to swarming bacterial colonies, cell migration, and embryonic morphogenesis (Farkas et al, 2002; Couzin & Krause, 2003; Waters & Bassler, 2005; Kawano et al, 2006; Szaboet al, 2006; Ballerini et al, 2008; Giardina, 2008; Friedl & Gilmour, 2009; Ullner et al, 2009; Zhang et al, 2010)

  • Population-level Dictyostelium signaling dynamics have been experimentally described in great detail (Martiel & Goldbeter, 1987; Laub & Loomis, 1998; Sawai et al, 2005; Gregor et al, 2010), but a comprehensive model that captures the basic phenomenology and yet retains predictive power is still missing

  • Through taking advantage of experimental advances that allow for quantitative measurements of intracellular cyclic AMP (cAMP) dynamics in response to a wide variety of extracellular cAMP stimuli and environmental conditions, we have developed a new conceptual framework for understanding collective behavior in cellular populations

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Summary

Introduction

Collective behavior is a common feature of many biological systems and is present in systems ranging from flocking birds, human spectators, schooling fish, and circadian rhythms in many higher organisms, to swarming bacterial colonies, cell migration, and embryonic morphogenesis (Farkas et al, 2002; Couzin & Krause, 2003; Waters & Bassler, 2005; Kawano et al, 2006; Szaboet al, 2006; Ballerini et al, 2008; Giardina, 2008; Friedl & Gilmour, 2009; Ullner et al, 2009; Zhang et al, 2010). In cellular systems that exhibit collective behavior, individual cells must coordinate their behavior with one another to produce the observed population-level phenomena and do so utilizing extracellular small molecules or proteins. Bacteria commonly utilize quorum-sensing molecules to synchronize gene expression in cellular populations and form aggregate biofilms (Waters & Bassler, 2005), and synthetic biology has exploited these mechanisms to engineer new circuits that give rise to population-level behaviors (Mondragon-Palomino et al, 2011; Youk & Lim, 2014). Illuminating how the dynamics of these intracellular networks lead to the population-wide collective behavior observed in these systems is a challenging problem, in part due to the difference in size and temporal scales at which these behaviors are controlled and displayed (Mehta & Gregor, 2010). We utilize the phenomenon of universality in an effort to connect individual genes to single-cell signaling behaviors and to relate singlecell activity to population behavior

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