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Newton's cradle: Cell cycle regulation by two mutually inhibitory oscillators.

Calin-Mihai Dragoi1, John J Tyson2, Béla Novák1

  • 1Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.

Mathematical Biosciences
|September 6, 2024
PubMed
Summary

This study presents a unified dynamical model for the cell division cycle, explaining its plasticity and diverse behaviors like cell cycle arrest and endoreplication through a control theory framework.

Keywords:
BistabilityCell cycleCheckpointsEndocyclesOscillations

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Area of Science:

  • Cell Biology
  • Systems Biology
  • Developmental Biology

Background:

  • The cell division cycle exhibits significant plasticity during development, transitioning from rapid embryonic divisions to size-controlled mitotic cycles.
  • Cells can pause, restart proliferation, or exit the cell cycle, and undergo variations like endoreplication (ploidy increase) or meiosis (ploidy decrease).

Purpose of the Study:

  • To unify diverse cell cycle mechanisms under a single dynamical paradigm using a control theoretical approach.
  • To model the cell cycle as a pair of mutually-inhibiting negative feedback oscillators controlling chromosome replication and segregation.

Main Methods:

  • Control theoretical framework to model the cell cycle.
  • Phase plane and bifurcation analysis to understand dynamical properties.
  • Physiologically realistic biochemical model to validate the regulatory structure.

Main Results:

  • The proposed framework reproduces fixed-period oscillations, variable-duration checkpoint arrests, and endocycles.
  • Phase plane and bifurcation analysis elucidate the dynamical basis of these cell cycle behaviors.
  • A single regulatory structure underlies the diverse functions of the cell cycle control network.

Conclusions:

  • A control theoretical dynamical paradigm unifies diverse cell cycle behaviors.
  • The cell cycle regulation can be conceptually analogized to Newton's cradle.