Modelling how plant cell-cycle progression leads to cell size regulation

Williamson, Daniel; Tasker-Brown, William; Murray, J.A.H.; Jones, Angharad R.; Band, Leah R.

Abstract

Populations of cells typically maintain a consistent size, despite cell division rarely being precisely symmetrical. Therefore, cells must possess a mechanism of “size control”, whereby the cell volume at birth affects cell-cycle progression. While size control mechanisms have been elucidated in a number of other organisms, it is not yet clear how this mechanism functions in plants. Here, we present a mathematical model of the key interactions in the plant cell cycle. Model simulations reveal that the network of interactions exhibits limit-cycle solutions, with biological switches underpinning both the G1/S and G2/M cell-cycle transitions. Embedding this network model within growing cells, we test hypotheses as to how cell-cycle progression can depend on cell size. We investigate two different mechanisms at both the G1/S and G2/M transitions: (i) differential expression of cell-cycle activator and inhibitor proteins (with synthesis of inhibitor proteins being independent of cell size), and (ii) equal inheritance of inhibitor proteins after cell division. The model demonstrates that both these mechanisms can lead to larger daughter cells progressing through the cell cycle more rapidly, and can thus contribute to cell-size control. To test how these features enable size homeostasis over multiple generations, we then simulated these mechanisms in a cell-population model with multiple rounds of cell division. These simulations suggested that integration of size-control mechanisms at both G1/S and G2/M provides long-term cell-size homeostasis. We concluded that while both size independence and equal inheritance of inhibitor proteins can reduce variations in cell size across individual cell-cycle phases, combining size-control mechanisms at both G1/S and G2/M is essential to maintain size homeostasis over multiple generations. Thus, our study reveals how features of the cell-cycle network enable cell-cycle progression to depend on cell size, and provides a mechanistic understanding of how plant cell populations maintain consistent size over generations.

Citation

Williamson, D., Tasker-Brown, W., Murray, J., Jones, A. R., & Band, L. R. (2023). Modelling how plant cell-cycle progression leads to cell size regulation. PLoS Computational Biology, 19(10), Article e1011503. https://doi.org/10.1371/journal.pcbi.1011503

• Journal Article Type: Article
• Acceptance Date: Sep 7, 2023
• Online Publication Date: Oct 20, 2023
• Publication Date: Oct 20, 2023
• Deposit Date: Sep 18, 2023
• Publicly Available Date: Oct 20, 2023
• Journal: PLoS Computational Biology
• Print ISSN: 1553-734X
• Electronic ISSN: 1553-7358
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 19
• Issue: 10
• Article Number: e1011503
• DOI: https://doi.org/10.1371/journal.pcbi.1011503
• Public URL: https://nottingham-repository.worktribe.com/output/25361565
• Publisher URL: https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1011503