The biomechanical properties of an epithelial tissue determine the location of its vasculature

• Published in: Nature communications 2016-12, Vol.7 (1), p.13560-13560, Article 13560
• Main Authors: Kragl, Martin, Schubert, Rajib, Karsjens, Haiko, Otter, Silke, Bartosinska, Barbara, Jeruschke, Kay, Weiss, Jürgen, Chen, Chunguang, Alsteens, David, Kuss, Oliver, Speier, Stephan, Eberhard, Daniel, Müller, Daniel J., Lammert, Eckhard
• Format: Article
• Language: English
• Subjects: 13/1; 13/109; 13/89; 38/90; 631/136/16; 631/80/79; 64/60; 82/29; Actomyosin - physiology; Animals; Apoptosis; Basement Membrane - physiology; Biomechanical Phenomena; Biomechanics; Blood vessels; Cell Adhesion - physiology; Cell growth; Diabetes; Endothelial Cells - cytology; Endothelial Cells - physiology; Epithelial Cells - physiology; Epithelium - blood supply; Epithelium - physiology; Female; Glucose; Glucose Intolerance - physiopathology; Humanities and Social Sciences; Insulin; Insulin - metabolism; Insulin Secretion; Islets of Langerhans - blood supply; Islets of Langerhans - cytology; Islets of Langerhans - physiology; Kinases; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Morphology; multidisciplinary; Neovascularization, Physiologic; Protein-Serine-Threonine Kinases - deficiency; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - physiology; Science; Science (multidisciplinary); Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms13560

An important question is how growing tissues establish a blood vessel network. Here we study vascular network formation in pancreatic islets, endocrine tissues derived from pancreatic epithelium. We find that depletion of integrin-linked kinase (ILK) in the pancreatic epithelial cells of mice results in glucose intolerance due to a loss of the intra-islet vasculature. In turn, blood vessels accumulate at the islet periphery. Neither alterations in endothelial cell proliferation, apoptosis, morphology, Vegfa expression and VEGF-A secretion nor ‘empty sleeves’ of vascular basement membrane are found. Instead, biophysical experiments reveal that the biomechanical properties of pancreatic islet cells, such as their actomyosin-mediated cortex tension and adhesive forces to endothelial cells, are significantly changed. These results suggest that a sorting event is driving the segregation of endothelial and epithelial cells and indicate that the epithelial biomechanical properties determine whether the blood vasculature invades or envelops a growing epithelial tissue. Vasculature is denser in soft than in stiff tissues. Kragl et al . suggest a mechanistic link between biomechanical tissue properties and vascularization by showing that integrin-linked kinase reduces the contractile forces of the cell cortex in endocrine pancreatic cells, facilitating their adhesion to blood vessels and enabling pancreatic islet vascularization.