Blood vessel tortuosity selects against evolution of aggressive tumor cells in confined tissue environments: A modeling approach
Fig 3
Simulations with mutating cells and stable vasculature.
Mutation rate = 10%. (a-b) Simulations initiated with non-mutating cells (green) and a single mutating cell (red) near (a) or far from (b) the nutrient source. The frames are from simulations where the mutating cell persisted and took over the population. (c-f) Results from simulations initiated with mutating cells. (c) Cell configuration at time t = 3000 MCS, showing intracellular pressure as the color code. Note the fluctuations in pressure distribution compared to the non-mutating case in Fig 2. (d) Population dynamics of a mutating population as a function of simulation time, showing the number of cells, intracellular pressure and tissue coverage. The number of cells initially increases and after a peak drops to almost half of the peak value, where it stabilizes. The intracellular pressure follows the initial increase in cell numbers. During the cell number drop the pressure is moderated to almost half, after which it is increasing to reach a plateau. The tissue coverage drops from the initial full coverage to approximately 50%. (e) Oxygen concentrations in the system at t = 3000 MCS. Nutrients are depleted further from the blood vessels, eventually resulting in a shortage of oxygen in distant regions. (f) Nutrient levels during the simulation reveal the depletion of glucose and oxygen during the expansion phase. A simultaneous increase in lactate levels shows the appearance of fermentors. When nutrients are depleted, the population size declines. With the decrease of respiration, oxygen levels return to the level observed in the non-mutating populations (Fig 2d). Plots show average of 10 independent simulations.