Allee effect in eukaryotic cell populations

The suspension culture of cells at provides an opportunity to study the multicellular life at low cell densities. In our earlier work with the model eukaryote Dictyostelium discoideum, we argued that the familiar but not understood transition from slow-to-fast growth at low cell densities (lag-log transition) was a collective, Allee effect during which cells communicate their density to one another by means of collisions. In this work, through improved protocols and assays, we put the phenomenon on a much firmer biological basis and show two new results. First, by means of variable shear rate experiments we prove that, in contrast to our previous conclusions, cell collisions are not responsible for the slow-to-fast growth transition. Second, we provide evidence that the transition is in fact caused by endocrine signaling – an unidentified molecule is secreted into the extracellular medium and used as a chemical signal. In order to interpret these results we developed a chemical signaling theory and calculated the expected cell density at the transition. This estimate agrees with observations, however within a broad range of theoretical uncertainty. Next, we estimate the experimentally observable variation in lag times at the transition, by considering the uncertainty in the inoculation density, possible variations due to asynchronous cell population and the fluctuations in receptor-ligand binding. None of these explanations are sufficient to explain the observed wide range of variation in lag times among identically prepared samples. PACS Classification: 87.17.Ee, 87.18.Fx