16 research outputs found
Multiscale modeling of oscillations and spiral waves in Dictyostelium populations
Unicellular organisms exhibit elaborate collective behaviors in response to
environmental cues. These behaviors are controlled by complex biochemical
networks within individual cells and coordinated through cell-to-cell
communication. Describing these behaviors requires new mathematical models that
can bridge scales -- from biochemical networks within individual cells to
spatially structured cellular populations. Here, we present a family of
multiscale models for the emergence of spiral waves in the social amoeba
Dictyostelium discoideum. Our models exploit new experimental advances that
allow for the direct measurement and manipulation of the small signaling
molecule cAMP used by Dictyostelium cells to coordinate behavior in cellular
populations. Inspired by recent experiments, we model the Dictyostelium
signaling network as an excitable system coupled to various pre-processing
modules. We use this family of models to study spatially unstructured
populations by constructing phase diagrams that relate the properties of
population-level oscillations to parameters in the underlying biochemical
network. We then extend our models to include spatial structure and show how
they naturally give rise to spiral waves. Our models exhibit a wide range of
novel phenomena including a density dependent frequency change, bistability,
and dynamic death due to slow cAMP dynamics. Our modeling approach provides a
powerful tool for bridging scales in modeling of Dictyostelium populations
Quantitative biology: where modern biology meets physical sciences
Quantitative methods and approaches have been playing an increasingly important role in cell biology in recent years. They involve making accurate measurements to test a predefined hypothesis in order to compare experimental data with predictions generated by theoretical models, an approach that has benefited physicists for decades. Building quantitative models in experimental biology not only has led to discoveries of counterintuitive phenomena but has also opened up novel research directions. To make the biological sciences more quantitative, we believe a two-pronged approach needs to be taken. First, graduate training needs to be revamped to ensure biology students are adequately trained in physical and mathematical sciences and vice versa. Second, students of both the biological and the physical sciences need to be provided adequate opportunities for hands-on engagement with the methods and approaches necessary to be able to work at the intersection of the biological and physical sciences. We present the annual Physiology Course organized at the Marine Biological Laboratory (Woods Hole, MA) as a case study for a hands-on training program that gives young scientists the opportunity not only to acquire the tools of quantitative biology but also to develop the necessary thought processes that will enable them to bridge the gap between these disciplines
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Eco-evolutionary significance of “loners”
International audienceLoners-individuals out of sync with a coordinated majority-occur frequently in nature. Are loners incidental byproducts of large-scale coordination attempts, or are they part of a mosaic of life-history strategies? Here, we provide empirical evidence of naturally occurring heritable variation in loner behavior in the model social amoeba Dictyostelium discoideum. We propose that Dictyostelium loners-cells that do not join the multicellular life stagearise from a dynamic population-partitioning process, the result of each cell making a stochastic, signal-based decision. We find evidence that this imperfectly synchronized multicellular development is affected by both abiotic (environmental porosity) and biotic (signaling) factors. Finally, we predict theoretically that when a pair of strains differing in their partitioning behavior coaggregate, cross-signaling impacts slime-mold diversity across spatiotemporal scales. Our findings suggest that loners could be critical to understanding collective and social behaviors, multicellular development, and ecological dynamics in D. discoideum. More broadly, across taxa, imperfect coordination of collective behaviors might be adaptive by enabling diversification of life-history strategies
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From intracellular signaling to population oscillations: bridging size- and time-scales in collective behavior
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