Pedro Barbacena

Blood vessel formation generates unique vascular patterns in each individual. The principles governing the apparent stochasticity of this process remain to be elucidated. Using mathematical methods, we find that the transition between two fundamental vascular morphogenetic programs – sprouting angiogenesis and vascular remodeling – is established by a shift on collective front-rear polarity of endothelial cells. We demonstrate that the competition between biochemical (VEGFA) and mechanical (blood flow-induced shear stress) cues controls this collective polarity shift. Shear stress increases tension at focal adhesions overriding VEGFA-driven collective polarization, which relies on tension at adherens junctions. We propose that vascular morphogenetic cues compete to regulate individual cell polarity and migration through tension shifts that translates into tissue-level emergent behaviors, ultimately leading to uniquely organized vascular patterns.

Significance: In this report, we describe how endothelial cells, the cells lining the interior of blood vessels, invade into tissues to form new vessels through sprouting angiogenesis. We found that endothelial cells use a specific lamellipodia-related membrane protrusion for invasion, which we termed dactylopodia. These protrusions have a special morphology, originate from filopodia, are linked to membrane-ruffling activity, and are specialized in invading into avascular extracellular matrix. Our work lays the foundations for drug discovery targeting sprouting angiogenesis.