Figure 2: Effector mechanism simulations of tip cell contribution.

(a–c) Sensitivity analyses of respectively E^FIL (a), E^COR (b) and E^ADH (c) as single mechanism governing tip cell competition, by varying over a wide range values of respectively k_FIL, k_COR and k_ADH. The results for both the 1:1 (full line) and 9:1 (dashed line) in silico PFKFB3^KD:WT (isPFKFB3^KD:isWT) mosaic sprouts are shown. The red and orange horizontal line depict the tip cell contribution of PFKFB3^KD cells, as obtained experimentally in respectively the 1:1 and 9:1 PFKFB3^KD:WT sprouts⁵. The combined 1:1 and 9:1 simulation results yielded one specific k value (see pink double-headed arrow) for every single effector mechanism. (d,e) Combinatorial E^FIL/COR, E^FIL/ADH, E^COR/ADH and E^ALL simulations of tip cell contribution in 1:1 (d) or 9:1 (e) isPFKFB3^KD:isWT mosaic sprouts, illustrating that for every combinatorial effector, k values for its contributing effectors could be obtained matching the competitive disadvantage for PFKFB3^KD cells as observed in the experimental PFKFB3^KD:WT EC spheroid competition data (experimental data (ED), n=30 spheroids from 3 donors). For each combinatorial effector, the same k values matched both the 1:1 (first bar in d) and 9:1 (first bar in e) experimental mosaic PFKFB3^KD:WT sprout data. The second bar in panel d and e shows the expected 50% (d) or 90% (e) contribution of isWT cells in 1:1 (d) or 9:1 (e) isWT:isWT sprouts. n=150; ***P<0.001, versus isWT:isWT. ‘NS’ (not significant) versus ED; Fisher’s exact test.