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1. An optimal regulation of fluxes dictates microbial growth in and out of steady state

   https://doi.org/10.7554/eLife.84878  

   Chure, Griffin; Cremer, Jonas (March 2023, eLife)

   Bitbol, Anne-Florence; Walczak; Aleksandra M (Ed.)

   Effective coordination of cellular processes is critical to ensure the competitive growth of microbial organisms. Pivotal to this coordination is the appropriate partitioning of cellular resources between protein synthesis via translation and the metabolism needed to sustain it. Here, we extend a low-dimensional allocation model to describe the dynamic regulation of this resource partitioning. At the core of this regulation is the optimal coordination of metabolic and translational fluxes, mechanistically achieved via the perception of charged- and uncharged-tRNA turnover. An extensive comparison with ≈ 60 data sets from Escherichia coli establishes this regulatory mechanism’s biological veracity and demonstrates that a remarkably wide range of growth phenomena in and out of steady state can be predicted with quantitative accuracy. This predictive power, achieved with only a few biological parameters, cements the preeminent importance of optimal flux regulation across conditions and establishes low-dimensional allocation models as an ideal physiological framework to interrogate the dynamics of growth, competition, and adaptation in complex and ever-changing environments. 

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2. Modeling the impact of single-cell stochasticity and size control on the population growth rate in asymmetrically dividing cells

   https://doi.org/10.1371/journal.pcbi.1009080  

   Barber, Felix; Min, Jiseon; Murray, Andrew W.; Amir, Ariel (June 2021, PLOS Computational Biology)

   Csikász-Nagy, Attila (Ed.)

   Microbial populations show striking diversity in cell growth morphology and lifecycle; however, our understanding of how these factors influence the growth rate of cell populations remains limited. We use theory and simulations to predict the impact of asymmetric cell division, cell size regulation and single-cell stochasticity on the population growth rate. Our model predicts that coarse-grained noise in the single-cell growth rate λ decreases the population growth rate, as previously seen for symmetrically dividing cells. However, for a given noise in λ we find that dividing asymmetrically can enhance the population growth rate for cells with strong size control (between a “sizer” and an “adder”). To reconcile this finding with the abundance of symmetrically dividing organisms in nature, we propose that additional constraints on cell growth and division must be present which are not included in our model, and we explore the effects of selected extensions thereof. Further, we find that within our model, epigenetically inherited generation times may arise due to size control in asymmetrically dividing cells, providing a possible explanation for recent experimental observations in budding yeast. Taken together, our findings provide insight into the complex effects generated by non-canonical growth morphologies. 

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3. Rich Dynamics of a General Producer–Grazer Interaction Model under Shared Multiple Resource Limitations

   https://doi.org/10.3390/app13074150  

   Phan, Tin; Elser, James J.; Kuang, Yang (April 2023, Applied Sciences)

   N/A (Ed.)

   Organism growth is often determined by multiple resources interdependently. However, growth models based on the Droop cell quota framework have historically been built using threshold formulations, which means they intrinsically involve single-resource limitations. In addition, it is a daunting task to study the global dynamics of these models mathematically, since they employ minimum functions that are non-smooth (not differentiable). To provide an approach to encompass interactions of multiple resources, we propose a multiple-resource limitation growth function based on the Droop cell quota concept and incorporate it into an existing producer–grazer model. The formulation of the producer’s growth rate is based on cell growth process time-tracking, while the grazer’s growth rate is constructed based on optimal limiting nutrient allocation in cell transcription and translation phases. We show that the proposed model captures a wide range of experimental observations, such as the paradox of enrichment, the paradox of energy enrichment, and the paradox of nutrient enrichment. Together, our proposed formulation and the existing threshold formulation provide bounds on the expected growth of an organism. Moreover, the proposed model is mathematically more tractable, since it does not use the minimum functions as in other stoichiometric models. 

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4. Catalytic growth in a shared enzyme pool ensures robust control of centrosome size

   https://doi.org/10.7554/eLife.92203.3  

   Banerjee, Deb Sankar; Banerjee, Shiladitya (February 2025, eLife)

   Accurate regulation of centrosome size is essential for ensuring error-free cell division, and dysregulation of centrosome size has been linked to various pathologies, including developmental defects and cancer. While a universally accepted model for centrosome size regulation is lacking, prior theoretical and experimental works suggest a centrosome growth model involving autocatalytic assembly of the pericentriolar material. Here, we show that the autocatalytic assembly model fails to explain the attainment of equal centrosome sizes, which is crucial for error-free cell division. Incorporating latest experimental findings into the molecular mechanisms governing centrosome assembly, we introduce a new quantitative theory for centrosome growth involving catalytic assembly within a shared pool of enzymes. Our model successfully achieves robust size equality between maturing centrosome pairs, mirroring cooperative growth dynamics observed in experiments. To validate our theoretical predictions, we compare them with available experimental data and demonstrate the broad applicability of the catalytic growth model across different organisms, which exhibit distinct growth dynamics and size scaling characteristics. 

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5. Metabolism Shapes the Cell

   https://doi.org/10.1128/JB.00039-17  

   Sperber, Anthony M.; Herman, Jennifer K.; Margolin, William (May 2017, Journal of Bacteriology)

   ABSTRACT More than 5 decades of work support the idea that cell envelope synthesis, including the inward growth of cell division, is tightly coordinated with DNA replication and protein synthesis through central metabolism. Remarkably, no unifying model exists to account for how these fundamentally disparate processes are functionally coupled. Recent studies demonstrate that proteins involved in carbohydrate and nitrogen metabolism can moonlight as direct regulators of cell division, coordinate cell division and DNA replication, and even suppress defects in DNA replication. In this minireview, we focus on studies illustrating the intimate link between metabolism and regulation of peptidoglycan (PG) synthesis during growth and division, and we identify the following three recurring themes. (i) Nutrient availability, not growth rate, is the primary determinant of cell size. (ii) The degree of gluconeogenic flux is likely to have a profound impact on the metabolites available for cell envelope synthesis, so growth medium selection is a critical consideration when designing and interpreting experiments related to morphogenesis. (iii) Perturbations in pathways relying on commonly shared and limiting metabolites, like undecaprenyl phosphate (Und-P), can lead to pleotropic phenotypes in unrelated pathways. 

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