Illustration of model configurations and workflow of simulations.

<p>(a) Cells are initialized as a monolayer with four endothelial cells (red) representing cross-section of blood vessels perpendicular to the plane of simulation. (b) Simulation workflow. In the initial regime nutrients are allowed to diffuse into the system to generate a steady-state distribution, during which cells metabolize without changing their size or phenotype. After the fields have stabilized, the simulation is started and is run in iterative cycles of Monte Carlo steps (MCS). After each MCS, each cell performs metabolic trafficking, and is probed for cell division. Upon division, a potential mutation event is triggered in the daughter cells. Inset: unbiased parameters from 10⁴ cells after <i>t</i> = 1, 5, 10, …, 5 × 10⁴ number of mutations are distributed uniformly in the algorithm.