Figure 3.

Extracellular non-linear positive feedback gives rise to cooperation and competition. (A) Left panel shows heat maps of the simulated normalized interaction index, C, for the entire range of activation signals (m₁, m₂) of two interacting cells. Color bar on the bottom right depicts C values. Different areas emerge, in which the cells cooperate or compete with each other over IL-2. The black lines show the threshold of activation for each cell if it was activated alone. Three representative scenarios are marked with a black dot and the corresponding B levels of the two interacting cells are shown in the right panel (red bars), compared to B levels when the cells are activated alone (blue bars). (I) Cell1, that would have been activated had it been alone, is activated alongside Cell2 which would not have passed the activation threshold had it been alone. In this case, the stronger cell utilizes the IL-2 of the weaker cell and increases its number of bound IL-2R. (II) Two cells that would not have been activated were they alone pool their IL-2 and as a result Cell1 that is activated more strongly is driven above threshold. (III) Two cells that are above threshold by their own are activated together. In this case, Cell2 that is activated more strongly depletes the IL-2 reservoir and thus pushes its neighbor beneath the activation threshold. (B) Simulated C values for two interacting cells in the case of a (hypothetical) linear feedback. In this case the interaction would always lead to mutual exclusion, resulting in the activation of the stronger cell (same color bar as in A).