Modeling homeostasis mechanisms that set the target cell size

Abstract How organisms maintain cell size homeostasis is a long-standing problem that remains unresolved, especially in multicellular organisms. Recent experiments in diverse animal cell types demonstrate that within a cell population, cellular proliferation is low for small and large cells, but hig...

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Autores principales:	Cesar A. Vargas-Garcia, Mikael Björklund, Abhyudai Singh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1df57102af1448cf878237b0ee1a021c
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spelling	oai:doaj.org-article:1df57102af1448cf878237b0ee1a021c2021-12-02T18:51:52ZModeling homeostasis mechanisms that set the target cell size10.1038/s41598-020-70923-02045-2322https://doaj.org/article/1df57102af1448cf878237b0ee1a021c2020-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-70923-0https://doaj.org/toc/2045-2322Abstract How organisms maintain cell size homeostasis is a long-standing problem that remains unresolved, especially in multicellular organisms. Recent experiments in diverse animal cell types demonstrate that within a cell population, cellular proliferation is low for small and large cells, but high at intermediate sizes. Here we use mathematical models to explore size-control strategies that drive such a non-monotonic profile resulting in the proliferation capacity being maximized at a target cell size. Our analysis reveals that most models of size control yield proliferation capacities that vary monotonically with cell size, and non-monotonicity requires two key mechanisms: (1) the growth rate decreases with increasing size for excessively large cells; and (2) cell division occurs as per the Adder model (division is triggered upon adding a fixed size from birth), or a Sizer-Adder combination. Consistent with theory, Jurkat T cell growth rates increase with size for small cells, but decrease with size for large cells. In summary, our models show that regulation of both growth and cell-division timing is necessary for size control in animal cells, and this joint mechanism leads to a target cell size where cellular proliferation capacity is maximized.Cesar A. Vargas-GarciaMikael BjörklundAbhyudai SinghNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-8 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cesar A. Vargas-Garcia Mikael Björklund Abhyudai Singh Modeling homeostasis mechanisms that set the target cell size
description	Abstract How organisms maintain cell size homeostasis is a long-standing problem that remains unresolved, especially in multicellular organisms. Recent experiments in diverse animal cell types demonstrate that within a cell population, cellular proliferation is low for small and large cells, but high at intermediate sizes. Here we use mathematical models to explore size-control strategies that drive such a non-monotonic profile resulting in the proliferation capacity being maximized at a target cell size. Our analysis reveals that most models of size control yield proliferation capacities that vary monotonically with cell size, and non-monotonicity requires two key mechanisms: (1) the growth rate decreases with increasing size for excessively large cells; and (2) cell division occurs as per the Adder model (division is triggered upon adding a fixed size from birth), or a Sizer-Adder combination. Consistent with theory, Jurkat T cell growth rates increase with size for small cells, but decrease with size for large cells. In summary, our models show that regulation of both growth and cell-division timing is necessary for size control in animal cells, and this joint mechanism leads to a target cell size where cellular proliferation capacity is maximized.
format	article
author	Cesar A. Vargas-Garcia Mikael Björklund Abhyudai Singh
author_facet	Cesar A. Vargas-Garcia Mikael Björklund Abhyudai Singh
author_sort	Cesar A. Vargas-Garcia
title	Modeling homeostasis mechanisms that set the target cell size
title_short	Modeling homeostasis mechanisms that set the target cell size
title_full	Modeling homeostasis mechanisms that set the target cell size
title_fullStr	Modeling homeostasis mechanisms that set the target cell size
title_full_unstemmed	Modeling homeostasis mechanisms that set the target cell size
title_sort	modeling homeostasis mechanisms that set the target cell size
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/1df57102af1448cf878237b0ee1a021c
work_keys_str_mv	AT cesaravargasgarcia modelinghomeostasismechanismsthatsetthetargetcellsize AT mikaelbjorklund modelinghomeostasismechanismsthatsetthetargetcellsize AT abhyudaisingh modelinghomeostasismechanismsthatsetthetargetcellsize
_version_	1718377373419700224

Modeling homeostasis mechanisms that set the target cell size

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