TY - JOUR

T1 - Entrainment of a cellular circadian oscillator by light in the presence of molecular noise

AU - Wang, Guanyu

AU - Peskin, Charles S.

N1 - Funding Information:
We thank the anonymous reviewers of this paper for their invaluable suggestions. G.W. was supported by a MacCracken Fellowship from New York University.
Publisher Copyright:
© 2018 American Physical Society.

PY - 2018/6/25

Y1 - 2018/6/25

N2 - In this paper, we consider a stochastic molecular circadian oscillator described by a sequence of biological reactions and its deterministic kinetics governed by a system of ordinary differential equations in the limit of large numbers of molecules. The oscillations in the model are generated by negative feedback regulation of a gene. The focus of this paper is the entrainment of the oscillator by a periodic light signal that affects the maximal transcription rate of the gene. We introduce two scalings of the model parameters that provide independent control over the natural frequency of the oscillator and the relative noise level. We study entrainment in two ways: by visualizing the stochastic limit cycle in various projections of the discrete phase space of the system and by evaluating the maximum of the normalized cross correlation of the light signal with the number of protein molecules in the cell. The visualization method ignores the phase of the oscillator, and we find in this way that entrainment has a subtle organizing effect on the limit cycle as a whole. The cross correlation results reveal an interval of natural frequencies of the oscillator surrounding the frequency of the light signal within which maximal entrainment occurs with rather sharp drops in entrainment at the edges of this interval. The width of the interval of maximal entrainment increases with the amplitude of the light signal. These statements are applicable both to the stochastic oscillator and to its deterministic limit, but the results are most clear-cut in the deterministic case and degrade from there as the relative noise level increases.

AB - In this paper, we consider a stochastic molecular circadian oscillator described by a sequence of biological reactions and its deterministic kinetics governed by a system of ordinary differential equations in the limit of large numbers of molecules. The oscillations in the model are generated by negative feedback regulation of a gene. The focus of this paper is the entrainment of the oscillator by a periodic light signal that affects the maximal transcription rate of the gene. We introduce two scalings of the model parameters that provide independent control over the natural frequency of the oscillator and the relative noise level. We study entrainment in two ways: by visualizing the stochastic limit cycle in various projections of the discrete phase space of the system and by evaluating the maximum of the normalized cross correlation of the light signal with the number of protein molecules in the cell. The visualization method ignores the phase of the oscillator, and we find in this way that entrainment has a subtle organizing effect on the limit cycle as a whole. The cross correlation results reveal an interval of natural frequencies of the oscillator surrounding the frequency of the light signal within which maximal entrainment occurs with rather sharp drops in entrainment at the edges of this interval. The width of the interval of maximal entrainment increases with the amplitude of the light signal. These statements are applicable both to the stochastic oscillator and to its deterministic limit, but the results are most clear-cut in the deterministic case and degrade from there as the relative noise level increases.

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U2 - 10.1103/PhysRevE.97.062416

DO - 10.1103/PhysRevE.97.062416

M3 - Article

C2 - 30011522

AN - SCOPUS:85049312162

VL - 97

JO - Physical Review E - Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics

JF - Physical Review E - Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics

SN - 1063-651X

IS - 6

M1 - 062416

ER -