Biphasic growth dynamics control cell division in Caulobacter crescentus

Banerjee, Shiladitya; Lo, Klevin; Daddysman, Matthew K.; Selewa, Alan; Kuntz, Thomas; Dinner, Aaron R.; Scherer, Norbert F.

doi:10.1038/nmicrobiol.2017.116

Cited by 46 publications

(71 citation statements)

References 25 publications

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“…Intermediate values would behave either sizer-(0 < a < 1) or timer-like (1 < a < 2). Equation (16) could in principle be solved by sampling the stochastic maps given in section 3. More effective, however, is to discretise it and solve the resulting set of linear equations numerically.…”

Section: Comparison Of Cell Size Distributionsmentioning

confidence: 99%

“…This is because the lineage statistics have the same division size controls ϕ (cf. Equations 4,16). In the following, we provide a quantitative analysis of these effects based on the cell size moments.…”

Section: Comparison Of Cell Size Distributionsmentioning

confidence: 99%

“…Many microbes, however, rather grow by a constant size from birth to division, called the adder control [3,[13][14][15]. Other mixed strategies may be described by sizer-or timer-like controls [9,15,16].…”

Section: Introductionmentioning

confidence: 99%

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Analysis of Cell Size Homeostasis at the Single-Cell and Population Level

Thomas

2018

Front. Phys.

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Growth pervades all areas of life from single cells to cell populations to tissues. Cell size often fluctuates significantly from cell to cell and from generation to generation. Here we present a unified framework to predict the statistics of cell size variations within a lineage tree of a proliferating population. We analytically characterize (i) the distributions of cell size snapshots, (ii) the distribution within a population tree, and (iii) the distribution of lineages across the tree. Surprisingly, these size distributions differ significantly from observing single cells in isolation. In populations, cells seemingly grow to different sizes, typically exhibit less cell-to-cell variability and often display qualitatively different sensitivities to cell cycle noise and division errors. We demonstrate the key findings using recent single-cell data and elaborate on the implications for the ability of cells to maintain a narrow size distribution and the emergence of different power laws in these distributions.

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Section: Comparison Of Cell Size Distributionsmentioning

confidence: 99%

Section: Comparison Of Cell Size Distributionsmentioning

confidence: 99%

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Analysis of Cell Size Homeostasis at the Single-Cell and Population Level

Thomas

2018

Front. Phys.

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“…Values of a between zero and one imply an adder-sizer mixture, and such combinatorial control of cell size have been proposed in many organisms [24,[26][27][28]. V m is the mean newborn size, and (3) However, this simplistic case is non-homeostatic, in the sense that, the variance in newborn size grows unboundedly over time in the presence of noise [29,30].…”

Section: Fitnessmentioning

confidence: 99%

Joint regulation of growth and division timing drives size homeostasis in proliferating animal cells

Singh

Vargas-García

Björklund

2017

Preprint

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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 the extent of growth and cellular proliferation (i.e., fitness) 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 fitness profile resulting in an optimal cell size. Our analysis reveals that if cell size grows exponentially or linearly over time, then fitness always varies monotonically with size irrespective of how timing of division is regulated. Furthermore, if the cell divides upon attaining a critical size (as in the Sizer or size-checkpoint model), then fitness always increases with size irrespective of how growth rate is regulated. These results show that while several size control models can maintain cell size homeostasis, they fail to predict the optimal cell size, and hence unable to explain why cells prefer a certain size. Interestingly, fitness maximization at an optimal size requires two key ingredients: 1) The growth rate decreases with increasing size for large enough cells; and 2) The cell size at the time of division is a function of the newborn size. The latter condition is consistent with the Adder paradigm for division control (division is triggered upon adding a fixed size from birth), or a Sizer-Adder combination. Consistent with theory, Jurkat T cell growth rates, as measured via oxygen consumption or mitochondrial activity, increase with size for small cells, but decrease with size for large cells. In summary, regulation of both growth and cell division timing is critical for size control in animal cells, and this joint-regulation leads to an optimal size where cellular fitness is maximized.Size control is a fundamental aspect of biology that is seen at every level of organization, but in most cases remains poorly understood [1-5]. One simple solution for size control is the Sizer or size-checkpoint model that couples cellcycle transitions to attainment of a minimum cell mass or size. An alternative solution is the Adder model, where cells add a fixed amount of size in each division cycle independent of daughter size. While strong evidence for an Adder has been reported in diverse prokaryotes [6][7][8][9][10][11][12][13][14][15][16], and budding yeast [17], it remains to be seen if similar size homeostasis mechanisms are at play in higher eukaryotes.Recent experiments in proliferating animal cells reveal an intriguing observation about cellular fitness that ties deeply into size control as this suggested why cells aim to maintain certain size. In [18], fitness was assayed by first sorting a cell population into several subpopulations based on size, and then measuring the net proliferation

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“…Many microbes, however, rather grow by a constant size from birth to division, called the adder control 3,[11][12][13] . Other mixed strategies may be described by sizer-or timer-like controls 8,13,14 .…”

Section: Introductionmentioning

confidence: 99%

Analysis of cell size homeostasis at the single-cell and population level

Thomas

2018

Preprint

View full text Add to dashboard Cite

Growth pervades all areas of life from single cells to cell populations to tissues. However, cell size often fluctuates significantly from cell to cell and from generation to generation. Here we present a unified framework to predict the statistics of cell size variations within a lineage tree of a proliferating population. We analytically characterise (i) the distributions of cell size snapshots, (ii) the distribution within a population tree, and (iii) the distribution of lineages across the tree. Surprisingly, these size distributions differ significantly from observing single cells in isolation. In populations, cells seemingly grow to different sizes, typically exhibit less cell-to-cell variability and often display qualitatively different sensitivities to cell cycle noise and division errors. We demonstrate the key findings using recent single-cell data and elaborate on the implications for the ability of cells to maintain a narrow size distribution and the emergence of different power laws in these distributions.

show abstract

Biphasic growth dynamics control cell division in Caulobacter crescentus

Cited by 46 publications

References 25 publications

Analysis of Cell Size Homeostasis at the Single-Cell and Population Level

Analysis of Cell Size Homeostasis at the Single-Cell and Population Level

Joint regulation of growth and division timing drives size homeostasis in proliferating animal cells

Analysis of cell size homeostasis at the single-cell and population level

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