scholarly journals Characterizing non-exponential growth and bimodal cell size distributions in Schizosaccharomyces pombe: an analytical approach

2021 ◽  
Author(s):  
Chen Jia ◽  
Abhyudai Singh ◽  
Ramon Grima
Keyword(s):  
Cell Cycle ◽  
Fission Yeast ◽  
Cell Size ◽  
Control Strategy ◽  
Size Control ◽  
Birth Size ◽  
Size Distributions ◽  
Cell Size Distribution ◽  
A Cell ◽  
Cell Size Control

Unlike many single-celled organisms, the growth of fission yeast cells within a cell cycle is not exponential. It is rather characterized by three distinct phases (elongation, septation and fission), each with a different growth rate. Experiments also show that the distribution of cell size in a lineage is often bimodal, unlike the unimodal distributions measured for the bacterium Escherichia coli. Here we construct a detailed stochastic model of cell size dynamics in fission yeast. The theory leads to analytic expressions for the cell size and the birth size distributions, and explains the origin of bimodality seen in experiments. In particular our theory shows that the left peak in the bimodal distribution is associated with cells in the elongation phase while the right peak is due to cells in the septation and fission phases. We show that the size control strategy, the variability in the added size during a cell cycle and the fraction of time spent in each of the three cell growth phases have a strong bearing on the shape of the cell size distribution. Furthermore we infer all the parameters of our model by matching the theoretical cell size and birth size distributions to those from experimental single cell time-course data for seven different growth conditions. Our method provides a much more accurate means of determining the cell size control strategy (timer, adder or sizer) than the standard method based on the slope of the best linear fit between the birth and division sizes. We also show that the variability in added size and the strength of cell size control of fission yeast depend weakly on the temperature but strongly on the culture medium.

scholarly journals Reprogramming Cdr2-Dependent Geometry-Based Cell Size Control in Fission Yeast

2019 ◽  
Vol 29 (2) ◽  
pp. 350-358.e4 ◽  
Author(s):  
Giuseppe Facchetti ◽  
Benjamin Knapp ◽  
Ignacio Flor-Parra ◽  
Fred Chang ◽  
Martin Howard
Keyword(s):  
Fission Yeast ◽  
Cell Size ◽  
Size Control ◽  
Cell Size Control

scholarly journals Cell-size regulation in budding yeast does not depend on linear accumulation of Whi5

2020 ◽  
Vol 117 (25) ◽  
pp. 14243-14250 ◽  
Author(s):  
Felix Barber ◽  
Ariel Amir ◽  
Andrew W. Murray
Keyword(s):  
Cell Cycle ◽  
Cell Size ◽  
Cell Cycle Regulation ◽  
Budding Yeast ◽  
Size Control ◽  
Size Distributions ◽  
Wild Type ◽  
Gal1 Promoter ◽  
The Mean ◽  
Cycle Regulation

Cells must couple cell-cycle progress to their growth rate to restrict the spread of cell sizes present throughout a population. Linear, rather than exponential, accumulation of Whi5, was proposed to provide this coordination by causing a higher Whi5 concentration in cells born at a smaller size. We tested this model using the inducibleGAL1promoter to make the Whi5 concentration independent of cell size. At an expression level that equalizes the mean cell size with that of wild-type cells, the size distributions of cells with galactose-induced Whi5 expression and wild-type cells are indistinguishable. Fluorescence microscopy confirms that the endogenous andGAL1promoters produce different relationships between Whi5 concentration and cell volume without diminishing size control in the G1 phase. We also expressed Cln3 from the GAL1 promoter, finding that the spread in cell sizes for an asynchronous population is unaffected by this perturbation. Our findings indicate that size control in budding yeast does not fundamentally originate from the linear accumulation of Whi5, contradicting a previous claim and demonstrating the need for further models of cell-cycle regulation to explain how cell size controls passage through Start.

scholarly journals Analysis of noise mechanisms in cell size control

2016 ◽  
Author(s):  
Saurabh Modi ◽  
Cesar A. Vargas-Garcia ◽  
Khem Raj Ghusinga ◽  
Abhyudai Singh
Keyword(s):  
Cell Size ◽  
Power Law ◽  
Caulobacter Crescentus ◽  
Control Strategies ◽  
Size Control ◽  
Cellular Growth ◽  
Power Law Distribution ◽  
Noise Sources ◽  
Cell Size Distribution ◽  
Cell Size Control

AbstractAt the single-cell level, noise features in multiple ways through the inherent stochasticity of biomolecular processes, random partitioning of resources at division, and fluctuations in cellular growth rates. How these diverse noise mechanisms combine to drive variations in cell size within an isoclonal population is not well understood. To address this problem, we systematically investigate the contributions of different noise sources in well-known paradigms of cell-size control, such as the adder (division occurs after adding a fixed size from birth) and the sizer (division occurs upon reaching a size threshold). Analysis reveals that variance in cell size is most sensitive to errors in partitioning of volume among daughter cells, and not surprisingly, this process is well regulated among microbes. Moreover, depending on the dominant noise mechanism, different size control strategies (or a combination of them) provide efficient buffering of intercellular size variations. We further explore mixer models of size control, where a timer phase precedes/follows an adder, as has been proposed inCaulobacter crescentus. While mixing a timer with an adder can sometimes attenuate size variations, it invariably leads to higher-order moments growing unboundedly over time. This results in the cell size following a power-law distribution with an exponent that is inversely dependent on the noise in the timer phase. Consistent with theory, we find evidence of power-law statistics in the tail ofC. crescentuscell-size distribution, but there is a huge discrepancy in the power-law exponent as estimated from data and theory. However, the discrepancy is removed after data reveals that the size added by individual newborns from birth to division itself exhibits power-law statistics. Taken together, this study provides key insights into the role of noise mechanisms in size homeostasis, and suggests an inextricable link between timer-based models of size control and heavy-tailed cell size distributions.

scholarly journals Quantitative examination of five stochastic cell-cycle and cell-size control models for Escherichia coli and Bacillus subtilis

2021 ◽  
Author(s):  
Guillaume Le Treut ◽  
Fangwei Si ◽  
Dongyang Li ◽  
Suckjoon Jun
Keyword(s):  
Experimental Data ◽  
Escherichia Coli ◽  
Cell Cycle ◽  
Bacillus Subtilis ◽  
Cell Size ◽  
Size Control ◽  
Statistical Analysis Method ◽  
Quantitative Examination ◽  
Cell Size Control ◽  
Bacterial Cell Cycle

We examine five quantitative models of the cell-cycle and cell-size control in Escherichia coli and Bacillus subtilis that have been proposed over the last decade to explain single-cell experimental data generated with high-throughput methods. After presenting the statistical properties of these models, we test their predictions against experimental data. Based on simple calculations of the defining correlations in each model, we first dismiss the stochastic Helmstetter-Cooper model and the Initiation Adder model, and show that both the Replication Double Adder and the Independent Double Adder model are more consistent with the data than the other models. We then apply a recently proposed statistical analysis method and obtain that the Independent Double Adder model is the most likely model of the cell cycle. By showing that the Replication Double Adder model is fundamentally inconsistent with size convergence by the adder principle, we conclude that the Independent Double Adder model is most consistent with the data and the biology of bacterial cell-cycle and cell-size control. Mechanistically, the Independent Adder Model is equivalent to two biological principles: (i) balanced biosynthesis of the cell-cycle proteins, and (ii) their accumulation to a respective threshold number to trigger initiation and division.

A bimolecular mechanism for the cell size control of the cell cycle

Biosystems ◽  
1983 ◽  
Vol 16 (3-4) ◽  
pp. 297-305 ◽  
Author(s):  
L. Alberghina ◽  
E. Martegani ◽  
L. Mariani ◽  
G. Bortolan
Keyword(s):  
Cell Cycle ◽  
Cell Size ◽  
Size Control ◽  
Cell Size Control ◽  
Bimolecular Mechanism

scholarly journals Quantitative Examination of Five Stochastic Cell-Cycle and Cell-Size Control Models for Escherichia coli and Bacillus subtilis

2021 ◽  
Vol 12 ◽  
Author(s):  
Guillaume Le Treut ◽  
Fangwei Si ◽  
Dongyang Li ◽  
Suckjoon Jun
Keyword(s):  
Experimental Data ◽  
Escherichia Coli ◽  
Cell Cycle ◽  
Bacillus Subtilis ◽  
Cell Size ◽  
Size Control ◽  
Statistical Analysis Method ◽  
Quantitative Examination ◽  
Cell Size Control ◽  
Bacterial Cell Cycle

We examine five quantitative models of the cell-cycle and cell-size control in Escherichia coli and Bacillus subtilis that have been proposed over the last decade to explain single-cell experimental data generated with high-throughput methods. After presenting the statistical properties of these models, we test their predictions against experimental data. Based on simple calculations of the defining correlations in each model, we first dismiss the stochastic Helmstetter-Cooper model and the Initiation Adder model, and show that both the Replication Double Adder (RDA) and the Independent Double Adder (IDA) model are more consistent with the data than the other models. We then apply a recently proposed statistical analysis method and obtain that the IDA model is the most likely model of the cell cycle. By showing that the RDA model is fundamentally inconsistent with size convergence by the adder principle, we conclude that the IDA model is most consistent with the data and the biology of bacterial cell-cycle and cell-size control. Mechanistically, the Independent Adder Model is equivalent to two biological principles: (i) balanced biosynthesis of the cell-cycle proteins, and (ii) their accumulation to a respective threshold number to trigger initiation and division.

scholarly journals Constriction rate modulation can drive cell size control and homeostasis inC. crescentus

2018 ◽  
Author(s):  
Ambroise Lambert ◽  
Aster Vanhecke ◽  
Anna Archetti ◽  
Seamus Holden ◽  
Felix Schaber ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Size ◽  
Caulobacter Crescentus ◽  
Size Control ◽  
Time Lapse ◽  
Structured Illumination ◽  
Structured Illumination Microscopy ◽  
Daughter Cells ◽  
Division Site ◽  
Cell Size Control

AbstractRod-shaped bacteria typically grow first via sporadic and dispersed elongation along their lateral walls, then via a combination of zonal elongation and constriction at the division site to form the poles of daughter cells. Although constriction comprises up to half of the cell cycle, its impact on cell size control and homeostasis has rarely been considered. To reveal the roles of cell elongation and constriction in bacterial size regulation during cell division, we captured the shape dynamics ofCaulobacter crescentuswith time-lapse structured illumination microscopy and used molecular markers as cell-cycle landmarks. We perturbed constriction rate using a hyperconstriction mutant or fosfomycin inhibition. We report that constriction rate contributes to both size control and homeostasis, by determining elongation during constriction, and by compensating for variation in pre-constriction elongation on a single-cell basis.

scholarly journals The reverse, but coordinated, roles of Tor2 (TORC1) and Tor1 (TORC2) kinases for growth, cell cycle and separase-mediated mitosis in Schizosaccharomyces pombe

Open Biology ◽  
2011 ◽  
Vol 1 (3) ◽  
pp. 110007 ◽  
Author(s):  
Nobuyasu Ikai ◽  
Norihiko Nakazawa ◽  
Takeshi Hayashi ◽  
Mitsuhiro Yanagida
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Schizosaccharomyces Pombe ◽  
Cell Size ◽  
Chromosome Segregation ◽  
Kinase Activity ◽  
Size Control ◽  
Phosphatidyl Inositol ◽  
Nutrient Utilization ◽  
A Cell

Target of rapamycin complexes (TORCs), which are vital for nutrient utilization, contain a catalytic subunit with the phosphatidyl inositol kinase-related kinase (PIKK) motif. TORC1 is required for cell growth, while the functions of TORC2 are less well understood. We show here that the fission yeast Schizosaccharomyces pombe TORC2 has a cell cycle role through determining the proper timing of Cdc2 Tyr15 dephosphorylation and the cell size under limited glucose, whereas TORC1 restrains mitosis and opposes securin–separase, which are essential for chromosome segregation. These results were obtained using the previously isolated TORC1 mutant tor2-L2048S in the phosphatidyl inositol kinase (PIK) domain and a new TORC2 mutant tor1-L2045D , which harbours a mutation in the same site. While mutated TORC1 and TORC2 displayed diminished kinase activity and FKBP12/Fkh1-dependent rapamycin sensitivity, their phenotypes were nearly opposite in mitosis. Premature mitosis and the G2–M delay occurred in TORC1 and TORC2 mutants, respectively. Surprisingly, separase/cut1—securin/cut2 mutants were rescued by TORC1/ tor2-L2048S mutation or rapamycin addition or even Fkh1 deletion, whereas these mutants showed synthetic defect with TORC2/ tor1-L2045D . TORC1 and TORC2 coordinate growth, mitosis and cell size control, such as Wee1 and Cdc25 do for the entry into mitosis.

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