Characterizing stochastic cell cycle dynamics in exponential growth

Abstract

Two powerful and complementary experimental approaches are commonly used to study the cell cycle and cell biology: One class of experiments characterizes the statistics (or demographics) of an unsynchronized exponentially-growing population, while the other captures cell cycle dynamics, either by time-lapse imaging of full cell cycles or in bulk experiments on synchronized populations. In this paper, we study the subtle relationship between observations in these two distinct experimental approaches. We begin with an existing model: a single-cell deterministic description of cell cycle dynamics where cell states (i.e. periods or phases) have precise lifetimes. We then generalize this description to a stochastic model in which the states have stochastic lifetimes, as described by arbitrary probability distribution functions. Our analyses of the demographics of an exponential culture reveal a simple and exact correspondence between the deterministic and stochastic models: The corresponding state lifetimes in the deterministic model are equal to the exponential mean of the lifetimes in the stochastic model. An important implication is therefore that the demographics of an exponential culture will be well-fit by a deterministic model even if the state timing is stochastic. Although we explore the implications of the models in the context of the Escherichia coli cell cycle, we expect both the models as well as the significance of the exponential-mean lifetimes to find many applications in the quantitative analysis of cell cycle dynamics in other biological systems.

The high-resolution in vivo measurement of replication fork velocity and pausing by lag-time analysis

“…In most systems, synchronization requires cell-cycle arrest, which introduces a significant potential for artifactual results [14]; whereas lag-time analysis probes dynamics in steady-state growth. Our own preliminary analysis suggests that the timing of initiation at a subset of loci in Saccharomyces cerevisiae is changed by the cell synchronization procedure relative to steady-state growth [38].…”