Inoculum-density dependent growth reveals inherent cooperative effects and stochasticity in cancer cell cultures

2017 
We document the initial-density dependence of the growth rate achieved by Jurkat cell cultures in a standard growth medium with fixed carrying capacity. As the density $N_0$ of the inoculum varies over 4 orders of magnitude, three distinct growth regimes appear. At small $N_0$, the growth rate $\lambda$ is roughly constant and displays small sample-to-sample variability. Upon increasing $N_0$, $\lambda$ increases slowly together with fluctuations. Finally, after peaking at an intermediate $N_0$, it gets smaller and more homogeneous across cultures as the inoculum density converges to the carrying capacity of the medium. A minimal, deterministic, population-based mathematical model explains the observed qualitative features assuming (in agreement with data) the presence of a weak positive correlation between cell density and proliferation rate. These results support the idea that cell cultures can preserve a memory of the initial condition, possibly via contact interactions or through metabolic coupling.
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