Dynamic bistable switches enhance robustness and accuracy of cell cycle transitions

PLoS Comput Biol. 2021 Jan 7;17(1):e1008231. doi: 10.1371/journal.pcbi.1008231. eCollection 2021 Jan.

Abstract

Bistability is a common mechanism to ensure robust and irreversible cell cycle transitions. Whenever biological parameters or external conditions change such that a threshold is crossed, the system abruptly switches between different cell cycle states. Experimental studies have uncovered mechanisms that can make the shape of the bistable response curve change dynamically in time. Here, we show how such a dynamically changing bistable switch can provide a cell with better control over the timing of cell cycle transitions. Moreover, cell cycle oscillations built on bistable switches are more robust when the bistability is modulated in time. Our results are not specific to cell cycle models and may apply to other bistable systems in which the bistable response curve is time-dependent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Cell Compartmentation / physiology
  • Cell Cycle / physiology*
  • Cell Nucleus / metabolism
  • Computational Biology
  • Feedback, Physiological / physiology
  • Models, Biological*
  • Proteins / metabolism
  • Signal Transduction / physiology

Substances

  • Proteins

Grants and funding

This work was supported by the Research Foundation Flanders (FWO, www.fwo.be) with individual support to J.R. and project support to L.G. (Grant GOA5317N) and the KU Leuven Research Fund (No. C14/18/084) to L.G. The computational resources and services used in this work were provided by the VSC (Flemish Supercomputer Center), funded by the Research Foundation Flanders (FWO) and the Flemish Government - department EWI. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.