Sep 5, 2014

Stochasticity of metabolism and growth at the single-cell level

Nature
Daniel J KivietSander J Tans

Abstract

Elucidating the role of molecular stochasticity in cellular growth is central to understanding phenotypic heterogeneity and the stability of cellular proliferation. The inherent stochasticity of metabolic reaction events should have negligible effect, because of averaging over the many reaction events contributing to growth. Indeed, metabolism and growth are often considered to be constant for fixed conditions. Stochastic fluctuations in the expression level of metabolic enzymes could produce variations in the reactions they catalyse. However, whether such molecular fluctuations can affect growth is unclear, given the various stabilizing regulatory mechanisms, the slow adjustment of key cellular components such as ribosomes, and the secretion and buffering of excess metabolites. Here we use time-lapse microscopy to measure fluctuations in the instantaneous growth rate of single cells of Escherichia coli, and quantify time-resolved cross-correlations with the expression of lac genes and enzymes in central metabolism. We show that expression fluctuations of catabolically active enzymes can propagate and cause growth fluctuations, with transmission depending on the limitation of the enzyme to growth. Conversely, growth fluctuation...Continue Reading

  • References26
  • Citations96

References

Mentioned in this Paper

Single-Cell Analysis
Metabolic Process, Cellular
Fluctuation
Stochastic Processes
Alkalescens-Dispar Group
Enzymes, antithrombotic
Time-Lapse Imaging
Lac Gene
Cell Enlargement
Process of Secretion

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