title: Bridging time scales in cellular decision making with a stochastic bistable switch.
abstract: BACKGROUND
  Cellular transformations which involve a significant phenotypical change of the cell's state use bistable biochemical switches as underlying decision systems. Some of these transformations act over a very long time scale on the cell population level, up to the entire lifespan of the organism.
  
  
  RESULTS
  In this work, we aim at linking cellular decisions taking place on a time scale of years to decades with the biochemical dynamics in signal transduction and gene regulation, occurring on a time scale of minutes to hours. We show that a stochastic bistable switch forms a viable biochemical mechanism to implement decision processes on long time scales. As a case study, the mechanism is applied to model the initiation of follicle growth in mammalian ovaries, where the physiological time scale of follicle pool depletion is on the order of the organism's lifespan. We construct a simple mathematical model for this process based on experimental evidence for the involved genetic mechanisms.
  
  
  CONCLUSIONS
  Despite the underlying stochasticity, the proposed mechanism turns out to yield reliable behavior in large populations of cells subject to the considered decision process. Our model explains how the physiological time constant may emerge from the intrinsic stochasticity of the underlying gene regulatory network. Apart from ovarian follicles, the proposed mechanism may also be of relevance for other physiological systems where cells take binary decisions over a long time scale.
authors.affiliation: Institute for Systems Theory and Automatic Control, Universität Stuttgart, Pfaffenwaldring 9, Stuttgart, Germany. waldherr@ist.uni-stuttgart.de
authors.forename: Steffen
authors.initials: S
authors.lastname: Waldherr
authors.forename: Jingbo
authors.initials: J
authors.lastname: Wu
authors.forename: Frank
authors.initials: F
authors.lastname: Allgöwer
mesh_terms: D002450:Cell Communication; D002468:Cell Physiological Phenomena; D005260:Female; D006801:Humans; D008954:Models, Biological; D009865:Oocytes / Q000166:cytology / Q000254:growth & development; D006080:Ovarian Follicle / Q000166:cytology / Q000254:growth & development; D015203:Reproducibility of Results; D013269:Stochastic Processes; D013997:Time Factors