Effect of fluctuating nutrient supplies on the tissue.
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(a) Number of cells at the end of simulations (t = 100,000 MCS), showing for simulations with different vessel tortuosities () and different cell mutation rates (μ). In simulations with healthy vessels (high switching probability ) a mutating cell population produces more cells than non-mutating ones. However, in simulations with erratic nutrient supply (with lower blocking probability ), the mutating populations die out more frequently than the non-mutating ones. At extreme erratic switching () 10 out of 10 mutating populations are extinct and even healthy ones start to die out (2 out of 10 simulations). Error bars indicate standard deviation of cell numbers from 10 repetitions. Values belonging to different simulations with the same mutation rate are connected and are slightly shifted on the x-axis for better visibility. (b) Average intracellular growth signal evolution in the population are not changed in simulations with different vessel blocking probabilities (mutation rate μ = 0.1%). This shows that the vessel blocking probability does not directly affect selection and progression speed. (c) The average intracellular growth signal in simulations with decreasing vessel blocking probability (, solid lines) in mutating (red, μ = 10%) and not mutating (blue, μ = 0%) populations. Cell-cell competition in mutating populations initially drives the growth parameters to a high value just as in the simulations with stable nutrient sources. When the blocking probability reaches the magnitude of and below, populations die out (dashed lines: percentage of simulations with living cells). (d) Population sizes in simulations with stable nutrient sources () and in simulations where the blocking probability is controlled by the cell density (), creating a feedback. In both cases the populations survive. The tissue coverage is approximately halved, making the vessel blocking probability approximately in the feedback simulations.