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A stochastic vs deterministic perspective on the timing of cellular events

Author

Listed:
  • Lucy Ham

    (University of Melbourne
    University of Melbourne)

  • Megan A. Coomer

    (University of Melbourne
    University of Melbourne)

  • Kaan Öcal

    (University of Edinburgh
    University of Melbourne)

  • Ramon Grima

    (University of Edinburgh)

  • Michael P. H. Stumpf

    (University of Melbourne
    University of Melbourne)

Abstract

Cells are the fundamental units of life, and like all life forms, they change over time. Changes in cell state are driven by molecular processes; of these many are initiated when molecule numbers reach and exceed specific thresholds, a characteristic that can be described as “digital cellular logic”. Here we show how molecular and cellular noise profoundly influence the time to cross a critical threshold—the first-passage time—and map out scenarios in which stochastic dynamics result in shorter or longer average first-passage times compared to noise-less dynamics. We illustrate the dependence of the mean first-passage time on noise for a set of exemplar models of gene expression, auto-regulatory feedback control, and enzyme-mediated catalysis. Our theory provides intuitive insight into the origin of these effects and underscores two important insights: (i) deterministic predictions for cellular event timing can be highly inaccurate when molecule numbers are within the range known for many cells; (ii) molecular noise can significantly shift mean first-passage times, particularly within auto-regulatory genetic feedback circuits.

Suggested Citation

  • Lucy Ham & Megan A. Coomer & Kaan Öcal & Ramon Grima & Michael P. H. Stumpf, 2024. "A stochastic vs deterministic perspective on the timing of cellular events," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49624-z
    DOI: 10.1038/s41467-024-49624-z
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    References listed on IDEAS

    as
    1. Avigdor Eldar & Michael B. Elowitz, 2010. "Functional roles for noise in genetic circuits," Nature, Nature, vol. 467(7312), pages 167-173, September.
    2. Zhixing Cao & Ramon Grima, 2018. "Linear mapping approximation of gene regulatory networks with stochastic dynamics," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    3. Christopher V. Rao & Denise M. Wolf & Adam P. Arkin, 2002. "Control, exploitation and tolerance of intracellular noise," Nature, Nature, vol. 420(6912), pages 231-237, November.
    4. Sabrina L. Spencer & Suzanne Gaudet & John G. Albeck & John M. Burke & Peter K. Sorger, 2009. "Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis," Nature, Nature, vol. 459(7245), pages 428-432, May.
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