Schematic of computational and experimental methods.

Fig 1A and 1B show the calibration of tumor and endothelial cell number and VEGF concentration to hemocytometer and ELISA measurements over time. Given the calibrated VEGF production and consumption rates, we inform our hybrid multiscale model, shown to Fig 1C, to confocal microscopy images of angiogenic sprouts, depicted in Fig 1D. We analyze the model globally, calibrating model parameters to summary statistics of the data, namely the sprout length and vascular density, and locally, calibrating the local stalk cell divide time to segmented vascular structures. This sequential approach, starting with protein concentration and cell number experiments to inform the hybrid model prior to integrating confocal microscopy images, allows us to utilize experimental data at multiple scales to inform the multiscale nature of the tumor angiogenesis model.