Emergent mechanical control of vascular morphogenesis.
Sci Adv
; 9(32): eadg9781, 2023 08 11.
Article
in En
| MEDLINE
| ID: mdl-37566656
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Mechanotransduction, Cellular
/
Endothelial Cells
Limits:
Animals
Language:
En
Journal:
Sci Adv
Year:
2023
Document type:
Article
Affiliation country:
United States