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Journal Article
An analytical theory of balanced cellular growth
2020
Overview
The biological fitness of microbes is largely determined by the rate with which they replicate their biomass composition. Mathematical models that maximize this balanced growth rate while accounting for mass conservation, reaction kinetics, and limits on dry mass per volume are inevitably non-linear. Here, we develop a general theory for such models, termed Growth Balance Analysis (GBA), which provides explicit expressions for protein concentrations, fluxes, and growth rates. These variables are functions of the concentrations of cellular components, for which we calculate marginal fitness costs and benefits that are related to metabolic control coefficients. At maximal growth rate, the net benefits of all concentrations are equal. Based solely on physicochemical constraints, GBA unveils fundamental quantitative principles of cellular resource allocation and growth; it accurately predicts the relationship between growth rates and ribosome concentrations in
E. coli
and yeast and between growth rate and dry mass density in
E. coli
.
Genome-scale models of microbial metabolism largely ignore reaction kinetics. Here, the authors develop a general mathematical framework for modeling cellular growth with explicit non-linear reaction kinetics and use it to glean insights into the principles of cellular resource allocation and growth.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
