title: Intrinsic noise and division cycle effects on an abstract biological oscillator.
abstract: Oscillatory dynamics are common in biological pathways, emerging from the coupling of positive and negative feedback loops. Due to the small numbers of molecules typically contained in cellular volumes, stochastic effects may play an important role in system behavior. Thus, for moderate noise strengths, stochasticity has been shown to enhance signal-to-noise ratios or even induce oscillations in a class of phenomena referred to as "stochastic resonance" and "coherence resonance," respectively. Furthermore, the biological oscillators are subject to influences from the division cycle of the cell. In this paper we consider a biologically relevant oscillator and investigate the effect of intrinsic noise as well as division cycle which encompasses the processes of growth, DNA duplication, and cell division. We first construct a minimal reaction network which can oscillate in the presence of large or negligible timescale separation. We then derive corresponding deterministic and stochastic models and compare their dynamical behaviors with respect to (i) the extent of the parameter space where each model can exhibit oscillatory behavior and (ii) the oscillation characteristics, namely, the amplitude and the period. We further incorporate division cycle effects on both models and investigate the effect of growth rate on system behavior. Our results show that in the presence but not in the absence of large timescale separation, coherence resonance effects result in extending the oscillatory region and lowering the period for the stochastic model. When the division cycle is taken into account, the oscillatory region of the deterministic model is shown to extend or shrink for moderate or high growth rates, respectively. Further, under the influence of the division cycle, the stochastic model can oscillate for parameter sets for which the deterministic model does not. The division cycle is also found to be able to resonate with the oscillator, thereby enhancing oscillation robustness. The results of this study can give valuable insight into the complex interplay between oscillatory intracellular dynamics and various noise sources, stemming from gene expression, cell growth, and division.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas 77005, USA. mstam@alumni.rice.edu
authors.forename: Michail
authors.initials: M
authors.lastname: Stamatakis
authors.forename: Nikos V
authors.initials: NV
authors.lastname: Mantzaris
mesh_terms: D001683:Biological Clocks; D002455:Cell Division; D049109:Cell Proliferation; D004261:DNA Replication; D008954:Models, Biological; D017711:Nonlinear Dynamics; D013269:Stochastic Processes; D013997:Time Factors