Abstract

BackgroundThe population growth rate is an important characteristic of any cell culture. During sustained experiments, the growth rate may vary due to competition or adaptation. For instance, in presence of a toxin or a drug, an increasing growth rate indicates that the cells adapt and become resistant. Consequently, time-dependent growth rates are fundamental to follow on the adaptation of cells to a changing evolutionary landscape. However, as there are no tools to calculate the time-dependent growth rate directly by cell counting, it is common to use only end point measurements of growth rather than tracking the growth rate continuously.ResultsWe present a computer program for inferring the growth rate over time in suspension cells using nothing but cell counts, which can be measured non-destructively. The program was tested on simulated and experimental data. Changes were observed in the initial and absolute growth rates, betraying resistance and adaptation.ConclusionsFor experiments where adaptation is expected to occur over a longer time, our method provides a means of tracking growth rates using data that is normally collected anyhow for monitoring purposes. The program and its documentation are freely available at https://github.com/Sandalmoth/ratrack under the permissive zlib license.

Highlights

  • The population growth rate is an important characteristic of any cell culture

  • Note for instance how all of the simulated samples in the constant growth rate case had a greater number of cells than they would on average, leading to a slightly overestimated growth rate

  • The methodology is capable of distinguishing both absolute changes in growth rate, and differences specific to initial growth

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Summary

Introduction

The population growth rate is an important characteristic of any cell culture. In presence of a toxin or a drug, an increasing growth rate indicates that the cells adapt and become resistant. Time-dependent growth rates are fundamental to follow on the adaptation of cells to a changing evolutionary landscape. Population growth rates are a core property of cell lines, and can be influenced by many factors. In controlled experiments, cell growth rates, i.e. how quickly the population size changes over time, may correlate with the presence of drugs or toxins [1], temperature [2], or particular genetic changes in the cells [3], and other factors. The cell growth rate is an especially useful variable to feed into models of how a culture will progress [4,5,6]. Suspension cells follow logistic growth to a decent approximation, and in that case growth rate could be derived via some form of logistic fitting.

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