When different types of cells compete in a confined space, those that remove waste the fastest stand a better chance of dominating their environment. Researchers at the Max Planck Institute for Dynamics and Self-Organization (MPI-DS) demonstrated in their model that not only a higher rate of net proliferation, but also the rapid removal of dead cells provides a competitive advantage. They mixed two populations of cells that differed only in the rate of debris removal and showed that, after a few generations, the population with the higher removal rate begins to dominate the confined space.
Biological organisms and tissues exhibit a constant turnover of cellular material; for example, to maintain tissue integrity, in case of tumor growth, or for the survival of bacterial communities. Intuitively, cell types that can proliferate faster or die less frequently in a given environment will dominate the confined space within an organism or compartment. “However, these traditional factors are still not the only ones that determine competitive fitness, if the remains left by dying cells are also taken into account,” says Ramin Golestanian, managing director of MPI-DS. In their study, researchers from the Physics of Living Matter department showed that cell types that are eliminated faster after death have an advantage that can make them the dominant species.
The scientists created a model to simulate growing cells that fill a limited amount of space until mechanical pressure builds and they reach a state where cell division and cell death balance each other. “We wanted to find out what effect dead matter has on the growth of a living system. To do this, we designed a simple model that is one of the first to explicitly consider the mechanical effects of dead cells,” said Yoav Pollack, first author of the study, describes the approach. “We then looked at two cell types that differed exclusively in the rate of dead matter removal and tracked the proportion of both populations over time. To our excitement, we saw a clear impact on overall fitness, leading to an advantage for the type of cell whose dead cells are eliminated more quickly,” he explains.
Make room for new cells
At first glance, the removal of dead material may seem disconnected from the formation of new cells, or even counterproductive, as it opens space for other species to invade. But the model shows that removing waste faster increases the number of living cells compared to dead ones. In general, this results in more responsive growth when a species is presented with opportunities for expansion. While this is of little consequence in a population of homogeneous cells of the same type, it does make a difference at the interface where different cell types compete for space. The population with the highest clearing rate is more likely to have a nearby living cell available to fill the vacant space through proliferation. In this way, the higher proportion of living cells gives a competitive advantage.
“In simplified terms, it could be said that cleaning and occupying a new space is more advantageous than keeping the space already occupied,” says group leader Philip Bittihn. “In certain cases, this new contribution to competition could also explain why biological tissues and organisms evolved to use specific cell-killing mechanisms, which are more efficient compared to alternatives,” he concludes.
As this effect has now been described for the first time, it opens up several new lines of investigation, such as looking at how much it contributes to overall fitness relative to other fitness factors. However, the model shows that cleaning up your mess really does pay off for the cells.
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