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Emergent mechanical control of vascular morphogenesis

Authors: Jordan Whisler; Somayeh Shahreza; Karin Schlegelmilch; Nil Ege; Yousef Javanmardi; Andrea Malandrino; Ayushi Agrawal; +22 Authors

Emergent mechanical control of vascular morphogenesis

Abstract

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.

Countries
Spain, United Kingdom, Italy
Keywords

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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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
views
OpenAIRE UsageCountsViews provided by UsageCounts
downloads
OpenAIRE UsageCountsDownloads provided by UsageCounts
31
Top 10%
Average
Top 1%
112
119
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gold