Statistics and simulation of growth of single bacterial cells: Illustrations with B. subtilis and E. coli

Johan H. Van Heerden, Hermannus Kempe, Anne Doerr, Timo Maarleveld, Niclas Nordholt, Frank J. Bruggeman*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

The inherent stochasticity of molecular reactions prevents us from predicting the exact state of single-cells in a population. However, when a population grows at steady-state, the probability to observe a cell with particular combinations of properties is fixed. Here we validate and exploit existing theory on the statistics of single-cell growth in order to predict the probability of phenotypic characteristics such as cell-cycle times, volumes, accuracy of division and cell-age distributions, using real-time imaging data for Bacillus subtilis and Escherichia coli. Our results show that single-cell growth-statistics can accurately be predicted from a few basic measurements. These equations relate different phenotypic characteristics, and can therefore be used in consistency tests of experimental single-cell growth data and prediction of single-cell statistics. We also exploit these statistical relations in the development of a fast stochastic-simulation algorithm of single-cell growth and protein expression. This algorithm greatly reduces computational burden, by recovering the statistics of growing cell-populations from the simulation of only one of its lineages. Our approach is validated by comparison of simulations and experimental data. This work illustrates a methodology for the prediction, analysis and tests of consistency of single-cell growth and protein expression data from a few basic statistical principles.

Original languageEnglish
Article number16094
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017

Funding

FJB acknowledges funding from the Netherlands Research Organisation (NWO-VIDI 864.11.011). We thank Maxim Moinat for extending the StochPy simulation package and Coco van Boxtel for initial fluorescence microscopy experiments and testing the image analysis, cell segmentation and tracking algorithms.

FundersFunder number
NWO-VIDI864.11.011
Netherlands Research Organisation

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