scholarly journals Invariance of initiation mass and predictability of cell size inEscherichia coli

2016 ◽  
Author(s):  
Fangwei Si ◽  
Dongyang Li ◽  
Sarah E. Cox ◽  
John T. Sauls ◽  
Omid Azizi ◽  
...  

SummaryIt is generally assumed that the allocation and synthesis of total cellular resources in microorganisms are uniquely determined by the growth conditions. Adaptation to a new physiological state leads to a change in cell size via reallocation of cellular resources. However, it has not been understood how cell size is coordinated with biosynthesis and robustly adapts to physiological states. We show that cell size inEscherichia colican be predicted for any steady-state condition by projecting all biosynthesis into three measurable variables representing replication initiation, replication-division cycle, and the global biosynthesis rate. These variables can be decoupled by selectively controlling their respective core biosynthesis using CRISPR interference and antibiotics, verifying our predictions that different physiological states can result in the same cell size. We performed extensive growth inhibition experiments, and discovered that cell size at replication initiation per origin, namely the initiation mass or “unit cell,” is remarkably invariant under perturbations targeting transcription, translation, ribosome content, replication kinetics, fatty acid and cell-wall synthesis, cell division, and cell shape. Based on this invariance and balanced resource allocation, we explain why the total cell size is the sum of all unit cells. These results provide an overarching framework with quantitative predictive power over cell size in bacteria.


2019 ◽  
Author(s):  
Guillaume Witz ◽  
Erik van Nimwegen ◽  
Thomas Julou

AbstractLiving cells proliferate by completing and coordinating two essential cycles, a division cycle that controls cell size, and a DNA replication cycle that controls the number of chromosomal copies in the cell. Despite lacking dedicated cell cycle control regulators such as cyclins in eukaryotes, bacteria such as E. coli manage to tightly coordinate those two cycles across a wide range of growth conditions, including situations where multiple nested rounds of replication progress simultaneously. Various cell cycle models have been proposed to explain this feat, but it has been impossible to validate them so far due to a lack of experimental tools for systematically testing their different predictions. Recently new insights have been gained on the division cycle through the study of the structure of fluctuations in growth, size, and division in individual cells. In particular, it was found that cell size appears to be controlled by an adder mechanism, i.e. the added volume between divisions is held approximately constant and fluctuates independently of growth rate and cell size at birth. However, how replication initiation is regulated and coupled to cell size control remains unclear, mainly due to scarcity of experimental measurements on replication initiation at the single-cell level. Here, we used time-lapse microscopy in combination with microfluidics to directly measure growth, division and replication in thousands of single E. coli cells growing in both slow and fast growth conditions. In order to compare different phenomenological models of the cell cycle, we introduce a statistical framework which assess their ability to capture the correlation structure observed in the experimental data. Using this in combination with stochastic simulations, our data indicate that, instead of thinking of the cell cycle as running from birth to division, the cell cycle is controlled by two adder mechanisms starting at the initiation of replication: the added volume since the last initiation event controls the timing of both the next division event and the next replication initiation event. Interestingly the double-adder mechanism identified in this study has recently been found to explain the more complex cell cycle of mycobacteria, suggesting shared control strategies across species.



1989 ◽  
Vol 53 (370) ◽  
pp. 257-262 ◽  
Author(s):  
D. D. Hogarth ◽  
J. E. T. Horne

AbstractA thin (100 m) cover of flat-lying, Recent, calcite-rich tuff at Ndale near Fort Portal, Uganda, unconformably overlies steeply dipping Precambrian metamorphic rocks. It is locally radioactive owing to uranium-rich pyrochlore minerals and lesser amounts of zircon, monazite, titanite, and an unidentified thorium phosphate. In one concentrate, four grains of uranpyrochlore and one grain of uranoan pyrochlore showed a positive linear correlation of Ti with U, and negative linear correlations of Ti with Na, F and Sr. Ta remained high and relatively constant [11 anal., ave. 14.5 (0.6)% Ta2O5]. In the same concentrate the composition of a separate grain of uranoan pyrochlore did not plot on these lines and Ta was comparatively low [2 anal., ave. 4.5 (0.3)% Ta2O5]. The data suggest two separate paths of differentiation. However, zoned grains were not observed. Unit cells were cubic with a = 10.351 ± 0.002 Å for a grain with 12.9% UO2tot and 10.333 ± 0.002 Å for a grain with 26.6% UO2tot. On heating in air the cell size decreased, possibly due to oxidation of U4+. The crystalline nature of these minerals can be attributed to a very young (4000–5000 yr) geological age.



Author(s):  
Mahmoud A. Alzahrani ◽  
Seung-Kyum Choi

With rapid developments and advances in additive manufacturing technology, lattice structures have gained considerable attention. Lattice structures are capable of providing parts with a high strength to weight ratio. Most work done to reduce computational complexity is concerned with determining the optimal size of each strut within the lattice unit-cells but not with the size of the unit-cell itself. The objective of this paper is to develop a method to determine the optimal unit-cell size for homogenous periodic and conformal lattice structures based on the strain energy of a given structure. The method utilizes solid body finite element analysis (FEA) of a solid counter-part with a similar shape as the desired lattice structure. The displacement vector of the lattice structure is then matched to the solid body FEA displacement results to predict the structure’s strain energy. This process significantly reduces the computational costs of determining the optimal size of the unit cell since it eliminates FEA on the actual lattice structure. Furthermore, the method can provide the measurement of relative performances from different types of unit-cells. The developed examples clearly demonstrate how we can determine the optimal size of the unit-cell based on the strain energy. Moreover, the computational cost efficacy is also clearly demonstrated through comparison with the FEA and the proposed method.



2013 ◽  
Vol 10 (2) ◽  
pp. 3241-3279
Author(s):  
J. A. Bonachela ◽  
S. D. Allison ◽  
A. C. Martiny ◽  
S. A. Levin

Abstract. The elemental ratios of marine phytoplankton emerge from complex interactions between the biotic and abiotic components of the ocean, and reflect the plastic response of individuals to changes in their environment. The stoichiometry of phytoplankton is, thus, dynamic and dependent on the physiological state of the cell. We present a theoretical model for the dynamics of the carbon, nitrogen and phosphorus contents of a phytoplankton population. By representing the regulatory processes controlling nutrient uptake, and focusing on the relation between nutrient content and protein synthesis, our model qualitatively replicates existing experimental observations for nutrient content and ratios. The population described by our model takes up nutrients in proportions that match the input ratios for a broad range of growth conditions. In addition, there are two zones of single-nutrient limitation separated by a wide zone of co-limitation. Within the co-limitation zone, a single point can be identified where nutrients are supplied in an optimal ratio. The existence of a wide co-limitation zone affects the standard picture for species competing for nitrogen and phosphorus, which shows here a much richer pattern. However, additional comprehensive laboratory experiments are needed to test our predictions. Our model contributes to the understanding of the global cycles of oceanic nitrogen and phosphorus, as well as the elemental ratios of these nutrients in phytoplankton populations.



Materials ◽  
2019 ◽  
Vol 12 (16) ◽  
pp. 2565 ◽  
Author(s):  
Royan J. D’Mello ◽  
Anthony M. Waas

Representative volume elements (RVEs) are commonly used to compute the effective elastic properties of solid media having repeating microstructure, such as fiber reinforced composites. However, for softening materials, an RVE could be problematic due to localization of deformation. Here, we address the effects of unit cell size and fiber packing on the transverse tensile response of fiber reinforced composites in the context of integrated computational materials engineering (ICME). Finite element computations for unit cells at the microscale are performed for different sizes of unit cells with random fiber packing that preserve a fixed fiber volume fraction—these unit cells are loaded in the transverse direction under tension. Salient features of the response are analyzed to understand the effects of fiber packing and unit cell size on the details of crack path, overall strength and also the shape of the stress-strain response before failure. Provision for damage accumulation/cracking in the matrix is made possible via the Bazant-Oh crack band model. The results suggest that the choice of unit cell size is more sensitive to strength and less sensitive to stiffness, when these properties are used as homogenized inputs to macro-scale models. Unit cells of smaller size exhibit higher strength and this strength converges to a plateau as the size of the unit cell increases. In this sense, since stiffness has also converged to a plateau with an increase in unit cell size, the converged unit cell size may be thought of as an RVE. Results in support of these insights are presented in this paper.



IAWA Journal ◽  
1989 ◽  
Vol 10 (4) ◽  
pp. 417-426 ◽  
Author(s):  
L.G. Vysotskaya ◽  
E.A. Vaganov

Radial cell size of conifers of three speeies: Pinus sylvestris, Larix sibirica, and Larix gmelinii from natural stands in the south of the Krasnoyarsk region (USSR) have been measured with a semi-automated device. The main factors responsible for cell size variation have been determined. These are: age, growth rate, soil moisture, climatic changes and endogenous rhythm of cell growth. Age greatly affects the radial cell size in trees up to 30 years old. Growth rate only affects radial tracheid diameter in narrow rings of 0 to 0.5 mm. The main components of variation: soil moisture, climatic factors and a cyclic component have been estimated for pines from three different conditions of moisture: moist, moderately moist and dry. It was shown, that under optimal growth conditions the contribution of the endogenous component was more or less equal to that of the climatic component.



2018 ◽  
Author(s):  
Nairita Maitra ◽  
Jayamani Anandhakumar ◽  
Heidi M. Blank ◽  
Craig D. Kaplan ◽  
Michael Polymenis

ABSTRACTThe question of what determines whether cells are big or small has been the focus of many studies because it is thought that such determinants underpin the coupling of cell growth with cell division. In contrast, what determines the overall pattern of how cell size is distributed within a population of wild type or mutant cells has received little attention. Knowing how cell size varies around a characteristic pattern could shed light on the processes that generate such a pattern and provide a criterion to identify its genetic basis. Here, we show that cell size values of wild type Saccharomyces cerevisiae cells fit a gamma distribution, in haploid and diploid cells, and under different growth conditions. To identify genes that influence this pattern, we analyzed the cell size distributions of all single-gene deletion strains in Saccharomyces cerevisiae. We found that yeast strains which deviate the most from the gamma distribution are enriched for those lacking gene products functioning in gene expression, especially those in transcription or transcription-linked processes. We also show that cell size is increased in mutants carrying altered activity substitutions in Rpo21p/Rpb1, the largest subunit of RNA polymerase II (Pol II). Lastly, the size distribution of cells carrying extreme altered activity Pol II substitutions deviated from the expected gamma distribution. Our results are consistent with the idea that genetic defects in widely acting transcription factors or Pol II itself compromise both cell size homeostasis and how the size of individual cells is distributed in a population.



eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Nikola Ojkic ◽  
Diana Serbanescu ◽  
Shiladitya Banerjee

Rod-shaped bacterial cells can readily adapt their lengths and widths in response to environmental changes. While many recent studies have focused on the mechanisms underlying bacterial cell size control, it remains largely unknown how the coupling between cell length and width results in robust control of rod-like bacterial shapes. In this study we uncover a conserved surface-to-volume scaling relation in Escherichia coli and other rod-shaped bacteria, resulting from the preservation of cell aspect ratio. To explain the mechanistic origin of aspect-ratio control, we propose a quantitative model for the coupling between bacterial cell elongation and the accumulation of an essential division protein, FtsZ. This model reveals a mechanism for why bacterial aspect ratio is independent of cell size and growth conditions, and predicts cell morphological changes in response to nutrient perturbations, antibiotics, MreB or FtsZ depletion, in quantitative agreement with experimental data.



2020 ◽  
Author(s):  
Qing Zhang ◽  
Zhichao Zhang ◽  
Hualin Shi

Sixty years ago, bacterial cell size was found as an exponential function of growth rate. Fifty years ago, a more general relationship was proposed, in which the cell mass was equal to the initiation mass multiplied by the ratio of the total time of the C and D periods to the doubling time. This relationship has recently been experimentally confirmed by perturbing doubling time, C period, D period or the initiation mass. However, the underlying molecular mechanism remains unclear. Here, we developed a mechanistic and kinetic model to describe how the initiator protein DnaA mediates the initiation of DNA replication in E. coli. In the model, we introduced an initiation probability function involving competitive binding of DnaA-ATP (active) and DnaA-ADP (inactive) at replication origin to determine the initiation of replication. In addition, we considered RNAP availability, ppGpp inhibition, DnaA autorepression, DnaA titration by chromosomal sites, hydrolysis of DnaA-ATP along with DNA replication, reactivation of DnaA-ADP and established a kinetic description of these DnaA regulatory processes. We simulated DnaA kinetics and obtained a self-consistent cell size and a regular DnaA oscillation coordinated with the cell cycle at steady state. The relationship between the cell size obtained by the simulation and the growth rate, C period, D period or initiation mass reproduces the results of the experiment. This model also predicts how the number of DnaA and the initiation mass vary with the perturbation parameters (including those reflecting the mutation or interference of DnaA regulatory processes), which is comparable to experimental data. The results suggest that the regulatory mechanisms of DnaA level and activity are associated with the invariance of initiation mass and the cell size general relationship for matching frequencies of replication initiation and cell division. This study may provide clues for concerted control of cell size and cell cycle in synthetic biology.



2021 ◽  
Vol 8 ◽  
Author(s):  
Godefroid Charbon ◽  
Belén Mendoza-Chamizo ◽  
Christopher Campion ◽  
Xiaobo Li ◽  
Peter Ruhdal Jensen ◽  
...  

During steady-state Escherichia coli growth, the amount and activity of the initiator protein, DnaA, controls chromosome replication tightly so that initiation only takes place once per origin in each cell cycle, regardless of growth conditions. However, little is known about the mechanisms involved during transitions from one environmental condition to another or during starvation stress. ATP depletion is one of the consequences of long-term carbon starvation. Here we show that DnaA is degraded in ATP-depleted cells. A chromosome replication initiation block is apparent in such cells as no new rounds of DNA replication are initiated while replication events that have already started proceed to completion.



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