A Generalized Adder for Cell Size Homeostasis: Effects on Stochastic Clonal Proliferation

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Author(s)Nieto, César
Author(s)Vargas-García, César Augusto
Author(s)Singh, Abhyudai
Date Accessioned2025-03-28T19:32:57Z
Date Available2025-03-28T19:32:57Z
Publication Date2025-03-21
DescriptionThis article was originally published in Biophysical Journal. The version of record is available at: https://doi.org/10.1016/j.bpj.2025.03.011. © 2025. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/. This article will be embargoed until 03/21/2026.
AbstractMeasurements of cell size dynamics have revealed phenomenological principles by which individual cells control their size across diverse organisms. One of the emerging paradigms of cell size homeostasis is the adder, where the cell cycle duration is established such that the cell size increase from birth to division is independent of the newborn cell size. We provide a mechanistic formulation of the adder considering that cell size follows any arbitrary non-exponential growth law. Our results show that the main requirement to obtain an adder regardless of the growth law (the time derivative of cell size) is that cell cycle regulators are produced at a rate proportional to the growth law and cell division is triggered when these molecules reach a prescribed threshold level. Among the implications of this generalized adder, we investigate fluctuations in the proliferation of single-cell derived colonies. Considering exponential cell size growth, random fluctuations in clonal size show a transient increase and then eventually decay to zero over time (i.e., clonal populations become asymptotically more similar). In contrast, several forms of non-exponential cell size dynamics (with adder-based cell size control) yield qualitatively different results: clonal size fluctuations monotonically increase over time reaching a non-zero value. These results characterize the interplay between cell size homeostasis at the single-cell level and clonal proliferation at the population level, explaining the broad fluctuations in clonal sizes seen in barcoded human cell lines.
SponsorAS acknowledges the support of NIH-NIGMS via grant R35GM148351.
CitationNieto, César, César Augusto Vargas-García, and Abhyudai Singh. “A Generalized Adder for Cell Size Homeostasis: Effects on Stochastic Clonal Proliferation.” Biophysical Journal. Accessed March 28, 2025. https://doi.org/10.1016/j.bpj.2025.03.011.
ISSN1542-0086
URLhttps://udspace.udel.edu/handle/19716/35985
Languageen_US
PublisherBiophysical Journal
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
TitleA Generalized Adder for Cell Size Homeostasis: Effects on Stochastic Clonal Proliferation
TypeArticle
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