Cell volume distributions reveal cell growth rates and division times

Abstract

A population of cells in culture displays a range of phenotypic responses even when those cells are derived from a single cell and are exposed to a homogeneous environment. Phenotypic variability can have a number of sources including the variable rates at which individual cells within the population grow and divide. We have examined how such variations contribute to population responses by measuring cell volumes within genetically identical populations of cells where individual members of the population are continuously growing and dividing, and we have derived a function describing the stationary distribution of cell volumes that arises from these dynamics. The model includes stochastic parameters for the variability in cell cycle times and growth rates for individual cells in a proliferating cell line. We used the model to analyze the volume distributions obtained for two different cell lines and one cell line in the absence and presence of aphidicolin, a DNA polymerase inhibitor. The derivation and application of the model allows one to relate the stationary population distribution of cell volumes to extrinsic biological noise present in growing and dividing cell cultures.