A stochastic vs deterministic perspective on the timing of cellular events

Lucy Ham, Megan A. Coomer, Kaan Öcal, Ramon Grima, Michael P.H. Stumpf*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Article number5286
Number of pages10
JournalNature Communications
Volume15
Issue number1
DOIs
Publication statusPublished - 20 Jun 2024

Keywords / Materials (for Non-textual outputs)

  • first-passage time
  • stochastic
  • deterministic
  • moments
  • event timing
  • molecular switch
  • gene regulation

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