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Open Access Research article

Bridging time scales in cellular decision making with a stochastic bistable switch

Steffen Waldherr*, Jingbo Wu and Frank Allgöwer

Author Affiliations

Institute for Systems Theory and Automatic Control, Universität Stuttgart, Pfaffenwaldring 9, Stuttgart, Germany

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BMC Systems Biology 2010, 4:108  doi:10.1186/1752-0509-4-108

Published: 9 August 2010

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, occuring 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.