A LATTICE-GAS CELLULAR AUTOMATON MODEL FOR IN VITRO SPROUTING ANGIOGENESIS

The mechanisms of sprout formation and branching during sprouting angiogenesis are only partially understood and mostly attributed to nonlocal signals mediated by the heterogeneous distribution of vascular endothelial growth factor (VEGF). Here, we show that purely local mechanisms can account for angiogenic network formation. In particular, we examine the effects of homogeneous stimulation by VEGF on local endothelial cell cell interactions and on interactions between endothelial cells and the microenvironment. We adopt a cell-based mathematical modeling approach (lattice-gas cellular automaton) and fit our model to image data obtained from in vitro experiments tailored to homogeneous conditions. This approach reveals the basal effects of (homogeneous) VEGF stimulation, in particular increased movement coordination and cell cell adhesion but no significant change in contact guidance and extracellular matrix remodeling.