{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:21:29Z","timestamp":1772173289884,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1011336","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T00:00:00Z","timestamp":1691539200000}}],"reference-count":72,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T00:00:00Z","timestamp":1690502400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2021YFF1200500"],"award-info":[{"award-number":["2021YFF1200500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Peking-Tsinghua Center for Life Sciences"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Accurate timing of division and size homeostasis is crucial for cells. A potential mechanism for cells to decide the timing of division is the differential scaling of regulatory protein copy numbers with cell size. However, it remains unclear whether such a mechanism can lead to robust growth and division, and how the scaling behaviors of regulatory proteins influence the cell size distribution. Here we study a mathematical model combining gene expression and cell growth, in which the cell-cycle activators scale superlinearly with cell size while the inhibitors scale sublinearly. The cell divides once the ratio of their concentrations reaches a threshold value. We find that the cell can robustly grow and divide within a finite range of the threshold value with the cell size proportional to the ploidy. In a stochastic version of the model, the cell size at division is uncorrelated with that at birth. Also, the more differential the cell-size scaling of the cell-cycle regulators is, the narrower the cell-size distribution is. Intriguingly, our model with multiple regulators rationalizes the observation that after the deletion of a single regulator, the coefficient of variation of cell size remains roughly the same though the average cell size changes significantly. Our work reveals that the differential scaling of cell-cycle regulators provides a robust mechanism of cell size control.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1011336","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T13:37:25Z","timestamp":1690551445000},"page":"e1011336","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Implications of differential size-scaling of cell-cycle regulators on cell size 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