The “hybrid extrinsic-intrinsic” model.

<p><b>A.</b> Cells migrate, divide and die under the same conditions as in the “extrinsic” and “intrinsic” models. The phenotypic switch of each cell is dependent on the local cell density as in the “extrinsic” model, but the cells encountering a favourable microenvironment undergo phenotypic change with probabilities p_AtoB and p_BtoA. B: Results of a typical simulation of the “hybrid” model during the growth phase and at equilibrium. Note the simultaneous presence of small clusters and dispersed single type A cells. p_AtoB = 0.7 and p_BtoA = 0.4. C: The distribution of the number of neighbours around the A and B cells (left and right respectively) in the hybrid model. The average number of neighbours and the standard deviation are indicated for each panel. Note the more dispersed distribution of type A cell neighbours. D: Analysis of the spatial distribution randomness of SP and MP cells using Ripley's L statistics. The upper panel shows the type A cell L-function (red line) with values larger than 0 and outside the range defined by the upper-and lower-envelope functions (black line) (this indicates significant clustering of type A cells at small R distances). The type B cells (green line) are randomly distributed, because the L(h) values are close to 0 at all scales (R).