Statistics and simulation of growth of single bacterial cells
Illustrations with B. subtilis and E. coli
Johan H. Van Heerden (Vrije Universiteit Amsterdam)
Hermannus Kempe (Swammerdam Institute for Life Sciences)
Anne Doerr (Vrije Universiteit Amsterdam, TU Delft - BN/Marileen Dogterom Lab)
Timo Maarleveld (Central Risk Management, Vrije Universiteit Amsterdam)
Niclas Nordholt (Federal Institute for Materials Research and Testing Berlin, Vrije Universiteit Amsterdam)
Frank J. Bruggeman (Vrije Universiteit Amsterdam)
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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.