Dynamical Allocation of Cellular Resources as an Optimal Control Problem: Novel Insights into Microbial Growth Strategies

Type Article
Date 2016-03
Language English
Author(s) Giordano Nils1, 2, Mairet FrancisORCID3, Gouze Jean-Luc3, Geiselmann Johannes1, 2, de Jong Hidde2
Affiliation(s) 1 : Université Grenoble Alpes, Laboratoire Interdisciplinaire de Physique (CNRS UMR 5588), Saint Martin d’Hères, France
2 : Inria, Grenoble - Rhône-Alpes research centre, Montbonnot, Saint Ismier Cedex, France
3 : Inria, Sophia-Antipolis Méditerranée research centre, Sophia-Antipolis Cedex, France
Source Plos Computational Biology (1553-734X), 2016-03 , Vol. 12 , N. 3 , P. e1004802 (1-28)
DOI 10.1371/journal.pcbi.1004802
WOS© Times Cited 58
Abstract

Microbial physiology exhibits growth laws that relate the macromolecular composition of the cell to the growth rate. Recent work has shown that these empirical regularities can be derived from coarse-grained models of resource allocation. While these studies focus on steady-state growth, such conditions are rarely found in natural habitats, where microorganisms are continually challenged by environmental fluctuations. The aim of this paper is to extend the study of microbial growth strategies to dynamical environments, using a self-replicator model. We formulate dynamical growth maximization as an optimal control problem that can be solved using Pontryagin's Maximum Principle. We compare this theoretical gold standard with different possible implementations of growth control in bacterial cells. We find that simple control strategies enabling growth-rate maximization at steady state are suboptimal for transitions from one growth regime to another, for example when shifting bacterial cells to a medium supporting a higher growth rate. A near-optimal control strategy in dynamical conditions is shown to require information on several, rather than a single physiological variable. Interestingly, this strategy has structural analogies with the regulation of ribosomal protein synthesis by ppGpp in the enterobacterium Escherichia coli. It involves sensing a mismatch between precursor and ribosome concentrations, as well as the adjustment of ribosome synthesis in a switch-like manner. Our results show how the capability of regulatory systems to integrate information about several physiological variables is critical for optimizing growth in a changing environment.

Full Text
File Pages Size Access
Publisher's official version 28 911 KB Open access
S1 Text. Model derivation and analysis. 7 139 KB Open access
S2 Text. Model parameters. 4 77 KB Open access
S3 Text. Solution of optimal control problem. 5 112 KB Open access
S4 Text. Kinetic model of the ppGpp system in Escherichia coli. 5 118 KB Open access
S1 Table. Parameter values of self-replicator model. 1 45 KB Open access
S1 Fig. Simple control strategies for the self-replicator of bacterial growth. 1 65 KB Open access
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