Comparison of Deterministic and Stochastic Regime in a Model for Cdc42 Oscillations in Fission Yeast

Bull Math Biol. 2019 May;81(5):1268-1302. doi: 10.1007/s11538-019-00573-5. Epub 2019 Feb 12.

Abstract

Oscillations occur in a wide variety of essential cellular processes, such as cell cycle progression, circadian clocks and calcium signaling in response to stimuli. It remains unclear how intrinsic stochasticity can influence these oscillatory systems. Here, we focus on oscillations of Cdc42 GTPase in fission yeast. We extend our previous deterministic model by Xu and Jilkine to construct a stochastic model, focusing on the fast diffusion case. We use SSA (Gillespie's algorithm) to numerically explore the low copy number regime in this model, and use analytical techniques to study the long-time behavior of the stochastic model and compare it to the equilibria of its deterministic counterpart. Numerical solutions suggest noisy limit cycles exist in the parameter regime in which the deterministic system converges to a stable limit cycle, and quasi-cycles exist in the parameter regime where the deterministic model has a damped oscillation. Near an infinite period bifurcation point, the deterministic model has a sustained oscillation, while stochastic trajectories start with an oscillatory mode and tend to approach deterministic steady states. In the low copy number regime, metastable transitions from oscillatory to steady behavior occur in the stochastic model. Our work contributes to the understanding of how stochastic chemical kinetics can affect a finite-dimensional dynamical system, and destabilize a deterministic steady state leading to oscillations.

Keywords: Biochemical oscillations; Cell polarity; Noise-induced phenomena; Stochastic model.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms
  • Cell Polarity
  • Computer Simulation
  • Fourier Analysis
  • Kinetics
  • Linear Models
  • Mathematical Concepts
  • Models, Biological*
  • Rho Guanine Nucleotide Exchange Factors / metabolism
  • Schizosaccharomyces / cytology
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Stochastic Processes
  • cdc42 GTP-Binding Protein / metabolism*

Substances

  • Rho Guanine Nucleotide Exchange Factors
  • Schizosaccharomyces pombe Proteins
  • cdc42 protein, S pombe
  • cdc42 GTP-Binding Protein