title: Modeling oscillations and spiral waves in Dictyostelium populations.
abstract: 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 cyclic adenosine monophosphate (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 preprocessing modules. We use this family of models to study spatially unstructured populations of "fixed" cells by constructing phase diagrams that relate the properties of population-level oscillations to parameters in the underlying biochemical network. We then briefly discuss an extension of our model that includes spatial structure and show how this naturally gives 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.
authors.affiliation: Physics Department, Boston University, Boston, Massachusetts, USA.
authors.forename: Javad
authors.initials: J
authors.lastname: Noorbakhsh
authors.affiliation: Joseph Henry Laboratories of Physics, Princeton University, Princeton, New Jersey, USA.|Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Schwab
authors.affiliation: Joseph Henry Laboratories of Physics, Princeton University, Princeton, New Jersey, USA.|Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.
authors.forename: Allyson E
authors.initials: AE
authors.lastname: Sgro
authors.affiliation: Joseph Henry Laboratories of Physics, Princeton University, Princeton, New Jersey, USA.|Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gregor
authors.affiliation: Physics Department, Boston University, Boston, Massachusetts, USA.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Mehta
mesh_terms: D000242:Cyclic AMP / Q000378:metabolism; D004023:Dictyostelium / Q000166:cytology*; D005110:Extracellular Space / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D015398:Signal Transduction
chemical_list: D000242:Cyclic AMP