A stochastic vs deterministic perspective on the timing of cellular events

Lucy Ham, Megan A. Coomer, Kaan Öcal, Ramon Grima and Michael P. H. Stumpf ()
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Lucy Ham: University of Melbourne
Megan A. Coomer: University of Melbourne
Kaan Öcal: University of Edinburgh
Ramon Grima: University of Edinburgh
Michael P. H. Stumpf: University of Melbourne

Nature Communications, 2024, vol. 15, issue 1, 1-10

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-49624-z

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