Abstract
Cell size control emerges from a regulated balance between the rates of cell growth and division. In bacteria, simple quantitative laws connect cellular growth rate to ribosome abundance. However, it remains poorly understood how translation regulates bacterial cell size and shape under growth perturbations. Here, we develop a whole-cell model for growth dynamics of rod-shaped bacteria that links ribosomal abundance with cell geometry, division control, and the extracellular environment. Our study reveals that cell size maintenance under nutrient perturbations requires a balanced trade-off between ribosomes and division protein synthesis. Deviations from this trade-off relationship are predicted under translation inhibition, leading to distinct modes of cell morphological changes, in agreement with single-cell experimental data on Escherichia coli. Furthermore, by calibrating our model with experimental data, we predict how combinations of nutrient-, translational-, and shape perturbations can be chosen to optimize bacterial growth fitness and antibiotic resistance.
Highlights
Cell size maintenance is essential for regulating cell physiology, function, and fitness (Young, 2006)
Cell Size Control Emerges from Nutrient-Dependent Trade-Off between Rates of Cellular Growth and Division Protein Synthesis To understand how bacterial cell size changes with the nutrientspecific growth rate, we develop a model for the allocation of ribosomal resources toward cell growth and division protein synthesis
Mechanistic Origin of Ribosomal Trade-Off between Growth and Division To understand the mechanistic origin of the ribosomal tradeoff between growth and division protein synthesis (Equation 4), we develop a model for allocation of ribosomal resources, extending the framework of Scott et al (2010)
Summary
Cell size maintenance is essential for regulating cell physiology, function, and fitness (Young, 2006). Maintaining a characteristic cell size necessitates an intricate balance between cell growth and division rates. How this balance is achieved in different growth conditions remains an outstanding question. It has been known for over six decades that bacteria modulate their size in response to changes in nutrient conditions. Single-cell data show deviations from the nutrient growth law in experiments altering cellular proteomics (Basan et al, 2015b; Si et al, 2017), leaving open the connection between cell size, growth rate, and protein synthesis
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