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Fig. 1 | BMC Systems Biology

Fig. 1

From: Tip cell overtaking occurs as a side effect of sprouting in computational models of angiogenesis

Fig. 1

Overview of the workflow. We studied the biological relevance and the driving mechanisms of tip cell overtaking. a As a first step, we asked whether tip cell overtaking can be a side effect of sprouting. We studied tip cell overtaking in two computational models of angiogenic sprouting (the contact inhibition model and cell the elongation model), with different sprouting dynamics. We quantified tip cell overtaking and cell kinetics during simulations of these models and compared the results with similar in vitro experiments of Arima et al. [6]. b As a next step, we asked if tip cell overtaking can be regulated by VEGF-Dll4-Notch signaling. We added a VEGF-Dll4-Notch signaling network to each cell in the two models of angiogenic sprouting. Simulations are initialized with spheroids that contain a mix of wild type (WT) cells and Vegfr2 +/− cells. Due to signaling, cells can switch between four phenotypes during sprouting: WT tip cell, WT stalk cell, Vegfr2 +/− tip cell, and Vegfr2 +/− stalk cell. At the end of the simulations we quantified the percentage of sprout tips that were occupied by WT cells and compared the simulation results to experimental results of Jakobsson et al. [5]

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