Determining cancer cells division strategy

Abstract

Heterogeneity in the size distribution of cancer cell populations has been recently linked to drug resistance and invasiveness. However, despite many progresses have been made in understanding how such heterogeneous size distributions arise in fast-proliferating cell types -like bacteria and yeast-, comprehensive investigations on cancer cell populations are still lacking mainly due to the difficulties of monitoring the proliferation of the time scales typical of mammalian cells. From a reductionist cell dynamics point of view, the strategies allowing size homeostasis are roughly grouped into three classes, \emph{i.e.} timer, sizer, or adder. These strategies are empirically distinguishable given the phenomenological measurable relationship between the cell size at birth and at division, which requires following the proliferation at the single-cell level. Here, we show how it is possible to infer the growth regime and division strategy of leukemia cell populations using live cell fluorescence labeling and flow cytometry in combination with a quantitative analytical model where both cell growth and division rates depend on powers of the cell size. Using our novel approach, we found that the dynamics of the size distribution of leukemia Jurkat T-cells is quantitatively reproduced by (i) a sizer-like division strategy, with (ii) division times following an Erlang distribution given by the sum of at least three independent exponentially-distributed times and (iii) fluctuations up to 15\% of the inherited fraction of size at division with respect to the mother cell size. Finally, we note that our experimental and theoretical apparatus can be easily extended to other cell types and environmental conditions, allowing for a comprehensive characterization of the growth and division model different cells can adopt.