Blood vessel tortuosity selects against evolution of aggressive tumor cells in confined tissue environments: A modeling approach
Fig 7
(a) Clonal expansion. Model configurations of the same population at t = 1500 MCS and t = 6000 MCS. Each cell is depicted with one of 256 different colors at time t = 1500 MCS, and the daughters inherit this color from that time point onwards. The population 4500 MCS later consists of the descendants of about a dozen of the initial cells. (b) Cell trajectories showing that cells flow outwards from the nutrient sources (indicated with black dots). (c) Trajectories from a setup with randomly placed vessels, showing that the outflow is determined by the placement of vessels. (d) The population segregates into independently evolving parts around the blood vessels. Color code shows the chemotaxis parameter for glucose (χg(i, t)) and the stiffness parameter λv(i, t) at t = 70 000 MCS. Cells around the same source are homogeneous, but are different from cells surrounding other sources. (e) Chemotaxis parameter (χg(i, t)) and stiffness parameter (λv(i, t)) values in the populations shown in (d) as the function of time. The four segregated parts clearly separate in their parameter values, and evolve almost independently. Vertical line denotes the time t = 70 000 MCS corresponding to the time of the configurations on (d). (e) Trajectories from a late population in the fluctuating system, showing the trajectories moving from one source to another. Movement direction is indicated with arrows. (g, h): Combined chemotaxis parameters (〈χ′(i, t)〉i = 〈χg(i, t) + χo(i, t) − χl(i, t)〉i) as a function of time in simulations with different vessel tortuosities at the first 20 000 MCS (g) and for the whole simulation time (h). The parameter is increasing in all simulation conditions, showing that nutrient detection is important for cell survival. In simulations with lower blocking probabilities the random selection introduced by the blocking and opening of the vessels results in a higher noise in the combined chemotaxis parameters average. Values averaged from 10 independent simulation runs for each condition.