Vasculogenesis and angiogenesis are essential in myriad physiological and pathological processes, including tumor growth, but their mechanics are poorly understood. In the first stages of vascular development endothelial cells elongate and form a network-like structure, called the primary capillary plexus, which subsequently remodels, with the size of the vacancies between ribbons of endothelial cells coarsening over time.
Our strategy for elucidating how endothelial cells form vascular networks, is to focus on individual cell behavior. We aim to reconstruct the minimal set of cell behaviors that suffices for vascular-like patterning. We have built a computational model of in vitro endothelial cell cultures. This model quantitatively reproduces in vitro capillary development and subsequent in vitro remodeling.
With the computer model we show that elongated cell morphology is key to reproducing temporally correct patterning and pattern coarsening, and we make some predictions on the physicochemical properties of the essential, secreted molecular signals. The model also reproduces aspects of sprouting angiogenesis from individual cell behavior. Thus our model helps us to elucidate how endothelial cell behavior can drive vascular patterning.
Once we have identified which endothelial cell behaviors are required to form vascular networks, we might go on and ask which sub-cellular processes and genes are responsible for these behaviors, how genetic mutations and pathological conditions affect it, and, eventually, how we could manipulate these cell behaviors pharmacologically.
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