Impact of Variability in Cell Cycle Periodicity on Cell Population Dynamics

Cell cycle synchronization has been pivotal in the development of our understanding of cell population dynamics. Intriguingly, when cells are released from a synchronized state, they do not maintain synchronized cell division and rapidly become asynchronous. Here, using a combination of experiments and model simulations, we investigate this process of "cell cycle desynchronization" in cervical cancer cells (HeLa) that are arrested at the G1/S boundary. We tracked DNA content overtime at regular intervals to monitor cell cycle progression and developed a custom auto-similarity function to quantify the convergence to asynchronicity. In parallel, using experimental data, we developed a single-cell phenomenological model that returns DNA concentration across the cell cycle stages from a desynchronizing cell population. Our simulations revealed that desynchronization is primarily sensitive to cell cycle variability. We tested this prediction by introducing lipopolysaccharide to increase cellular noise, which resulted in greater cell cycle variability with an enhanced rate of desynchronization. Our results show that the desynchronization rate of cell populations can be used a proxy of the degree of variance in cell cycle periodicity.