Experimental and model-predicted fraction of Ki67 positive cells (left) and Collagen IV (ECM) density (right) for [G] = 25mM, [O] = 0.28mM at day 17 (red) and day 24 (green) vs. distance from the spheroid surface.

A deterministic cell cycle progression depending on the distance of a cell from the surface, generates sharp transitions that are experimentally not observed (left, dotted line), while a probabilistic transition generates a smooth monotonically decreasing function of Ki67 positive cells in the simulations (left, dashed). If in addition cells can progress in the cell cycle only if the local concentration of ECM overcomes a threshold value [ECM]min, the experimentally found Ki67 profile is recovered (left, full line). Right full line: ECM concentration in the computer simulation.