A nematic framework for sprouting angiogenesis

Sprouting angiogenesis is critical for embryogenesis, wound healing, and tumor growth. Here, we show that the liquid crystal framework, which has recently been leveraged to study various morphogenetic events, provides unique insight into angiogenic sprouting. In response to vascular endothelial growth factor, a potent proangiogenic factor, endothelial cells cultured on the surfaces of soft collagen hydrogels form elongated cell streams that coexist with more polygonal cell regions. Angiogenic sprouting initiates preferentially at cell stream tips, where nematic order gradients are most pronounced. We demonstrate that cell streams are associated with large traction forces that lead to three-dimensional deformations of the underlying hydrogel and that stream formation results from a delicate balance between microtubule polymerization and actomyosin contractility. Last, we show that active control of nematic order allows modulation of sprout formation, highlighting the key role of endothelial cell orientation gradients in angiogenic sprouting and paving the way for new therapeutic avenues.