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Vascularization is driven by morphogen signals and mechanical cues that coordinately regulate cellular force generation, migration, and shape change to sculpt the developing vascular network. However, it remains unclear whether developing vasculature actively regulates its own mechanical properties to achieve effective vascularization. We engineered tissue constructs containing endothelial cells and fibroblasts to investigate the mechanics of vascularization. Tissue stiffness increases during vascular morphogenesis resulting from emergent interactions between endothelial cells, fibroblasts, and ECM and correlates with enhanced vascular function. Contractile cellular forces are key to emergent tissue stiffening and synergize with ECM mechanical properties to modulate the mechanics of vascularization. Emergent tissue stiffening and vascular function rely on mechanotransduction signaling within fibroblasts, mediated by YAP1. Mouse embryos lacking YAP1 in fibroblasts exhibit both reduced tissue stiffness and develop lethal vascular defects. Translating our findings through biology-inspired vascular tissue engineering approaches will have substantial implications in regenerative medicine.
Model organisms, 570, Human Biology & Physiology, Tissue Engineering, Morfogènesi, 610, Endothelial Cells, Cell Differentiation, Cell Biology, Tumour Biology, Mechanotransduction, Cellular, Àrees temàtiques de la UPC::Enginyeria biomèdica, Extracellular Matrix, Imaging, Mice, Morphogenesis, Animals, Biomedicine and Life Sciences
Model organisms, 570, Human Biology & Physiology, Tissue Engineering, Morfogènesi, 610, Endothelial Cells, Cell Differentiation, Cell Biology, Tumour Biology, Mechanotransduction, Cellular, Àrees temàtiques de la UPC::Enginyeria biomèdica, Extracellular Matrix, Imaging, Mice, Morphogenesis, Animals, Biomedicine and Life Sciences
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