Fluctuations in tissue growth portray homeostasis as a critical state and long-time non-Markovian cell proliferation as Markovian

Lavalle, Natalia G.; Chara, Osvaldo; Grigera, Tomás S.

Abstract

Tissue growth is an emerging phenomenon that results from the cell-level interplay between proliferation and apoptosis, which is crucial during embryonic development, tissue regeneration, as well as in pathological conditions such as cancer. In this theoretical article, we address the problem of stochasticity in tissue growth by first considering a minimal Markovian model of tissue size, quantified as the number of cells in a simulated tissue, subjected to both proliferation and apoptosis. We find two dynamic phases, growth and decay, separated by a critical state representing a homeostatic tissue. Since the main limitation of the Markovian model is its neglect of the cell cycle, we incorporated a refractory period that temporarily prevents proliferation immediately following cell division, as a minimal proxy for the cell cycle, and studied the model in the growth phase. Importantly, we obtained from this last model an effective Markovian rate, which accurately describes general trends of tissue size. This study shows that the dynamics of tissue growth can be theoretically conceptualized as a Markovian process where homeostasis is a critical state flanked by decay and growth phases. Notably, in the growing non-Markovian model, a Markovian-like growth process emerges at large time scales.

Citation

Lavalle, N. G., Chara, O., & Grigera, T. S. (2023). Fluctuations in tissue growth portray homeostasis as a critical state and long-time non-Markovian cell proliferation as Markovian. Royal Society Open Science, 10(9), Article 230871. https://doi.org/10.1098/rsos.230871

• Journal Article Type: Article
• Acceptance Date: Aug 24, 2023
• Online Publication Date: Sep 13, 2023
• Publication Date: 2023-09
• Deposit Date: Sep 5, 2024
• Publicly Available Date: Sep 13, 2024
• Journal: Royal Society Open Science
• Electronic ISSN: 2054-5703
• Publisher: The Royal Society
• Peer Reviewed: Peer Reviewed
• Volume: 10
• Issue: 9
• Article Number: 230871
• DOI: https://doi.org/10.1098/rsos.230871
• Keywords: tissue, cell proliferation, non-Markovian model, time correlations, Markovian model
• Public URL: https://nottingham-repository.worktribe.com/output/25345007
• Publisher URL: https://royalsocietypublishing.org/doi/10.1098/rsos.230871