Inheritance of Cell-Cycle Duration in the Presence of Periodic Forcing

Noga Mosheiff*, Bruno M.C. Martins, Sivan Pearl-Mizrahi, Alexander Grünberger, Stefan Helfrich, Irina Mihalcescu, Dietrich Kohlheyer, James C.W. Locke, Leon Glass, Nathalie Q. Balaban

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Periodic forcing of nonlinear oscillators leads to a large number of dynamic behaviors. The coupling of the cell cycle to the circadian clock provides a biological realization of such forcing. A previous model of forcing leads to nontrivial relations between correlations along cell lineages. Here, we present a simplified two-dimensional nonlinear map for the periodic forcing of the cell cycle. Using high-throughput single-cell microscopy, we have studied the correlations between cell-cycle duration in discrete lineages of several different organisms, including those with known coupling to a circadian clock and those without known coupling to a circadian clock. The model reproduces the paradoxical correlations and predicts new features that can be compared with the experimental data. By fitting the model to the data, we extract the important parameters that govern the dynamics. Interestingly, the model reproduces bimodal distributions for cell-cycle duration, as well as the gating of cell division by the phase of the clock, without having been explicitly fed into the model. In addition, the model predicts that circadian coupling may increase cell-to-cell variability in a clonal population of cells. In agreement with this prediction, deletion of the circadian clock reduces variability. Our results show that simple correlations can identify systems under periodic forcing and that studies of nonlinear coupling of biological oscillators provide insight into basic cellular processes of growth.

Original languageAmerican English
Article number021035
JournalPhysical Review X
Volume8
Issue number2
DOIs
StatePublished - 9 May 2018

Bibliographical note

Publisher Copyright:
© 2018 authors. Published by the American Physical Society.

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