Spatial patterning of the Notch ligand Dll4 controls endothelial sprouting in vitro
| Autor: | Cecilia Sahlgren, L.A. Tiemeijer, Oscar M. J. A. Stassen, Jean-Philippe Frimat, Carlijn V. C. Bouten |
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| Přispěvatelé: | Soft Tissue Biomech. & Tissue Eng., Microsystems, Cell-Matrix Interact. Cardiov. Tissue Reg., Group Luttge |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Endothelium Angiogenesis Microfluidics lcsh:Medicine Neovascularization Physiologic Ligands Article Neovascularization 03 medical and health sciences Calcium-binding protein medicine Human Umbilical Vein Endothelial Cells Humans lcsh:Science Adaptor Proteins Signal Transducing Multidisciplinary Chemistry lcsh:R Calcium-Binding Proteins Hedgehog signaling pathway Cell biology Endothelial stem cell 030104 developmental biology medicine.anatomical_structure cardiovascular system Intercellular Signaling Peptides and Proteins lcsh:Q Endothelium Vascular medicine.symptom Signal transduction Sprouting Signal Transduction |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-10 (2018) Scientific Reports, 8(1):6392. Nature Publishing Group |
| ISSN: | 2045-2322 |
| Popis: | Angiogenesis, the formation of new blood vessels, is a vital process for tissue growth and development. The Notch cell-cell signalling pathway plays an important role in endothelial cell specification during angiogenesis. Dll4 - Notch1 signalling directs endothelial cells into migrating tip or proliferating stalk cells. We used the directing properties of Dll4 to spatially control endothelial cell fate and the direction of endothelial sprouts. We created linear arrays of immobilized Dll4 using micro contact printing. HUVECs were seeded perpendicular to these Dll4 patterns using removable microfluidic channels. The Notch activating properties of surface immobilized Dll4 were confirmed by qPCR. After induction of sprouting, microscopic images of fluorescently labelled endothelial sprouts were analysed to determine the direction and the efficiency of controlled sprouting (Ecs). Directionality analysis of the sprouts showed the Dll4 pattern changes sprout direction from random to unidirectional. This was confirmed by the increase of Ecs from 54.5 ± 3.1% for the control, to an average of 84.7 ± 1.86% on the Dll4 patterned surfaces. Our data demonstrates a surface-based method to spatially pattern Dll4 to gain control over endothelial sprout location and direction. This suggests that spatial ligand patterning can be used to provide control over (neo) vascularization. |
| Databáze: | OpenAIRE |
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