Intercellular Tension Negatively Regulates Angiogenic Sprouting of Endothelial Tip Cells via Notch1-Dll4 Signaling

Shue Wang, Jian Sun, Yuan Xiao, Yi Lu, Donna Zhang, Pak Kin Wong

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Mechanical force plays pivotal roles in vascular development during tissue growth and regeneration. Nevertheless, the process by which mechanical force controls the vascular architecture remains poorly understood. Using a systems bioengineering approach, it is shown that intercellular tension negatively regulates tip cell formation via Notch1-Dll4 signaling in mouse retinal angiogenesis in vivo, sprouting embryoid bodies, and human endothelial cell networks in vitro. Reducing the intercellular tension pharmacologically by a Rho-associated protein kinase inhibitor or physically by single cell photothermal ablation of the capillary networks promotes the expression of Dll4, enhances angiogenic sprouting of tip cells, and increases the vascular density. Computational biomechanics, RNA interference, and single cell gene expression analysis reveal that a reduction of intercellular tension attenuates the inhibitory effect of Notch signaling on tip cell formation and induces angiogenic sprouting. Taken together, the results reveal a mechanoregulation scheme for the control of vascular architecture by modulating angiogenic tip cell formation via Notch1-Dll4 signaling.

Original languageEnglish (US)
Article number1600019
JournalAdvanced Biosystems
Volume1
Issue number1-2
DOIs
StatePublished - Feb 1 2017

Fingerprint

Endothelial Cells
Blood Vessels
Biomechanics
Endothelial cells
Force control
Protein Kinase Inhibitors
Ablation
RNA
Gene expression
Mechanical Phenomena
Tissue
Embryoid Bodies
Proteins
Bioengineering
rho-Associated Kinases
RNA Interference
Biomechanical Phenomena
Regeneration
Gene Expression
Growth

Keywords

  • angiogenesis
  • mechanoregulation
  • nanoparticles
  • notch signaling
  • tip cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biomaterials
  • Biomedical Engineering

Cite this

Intercellular Tension Negatively Regulates Angiogenic Sprouting of Endothelial Tip Cells via Notch1-Dll4 Signaling. / Wang, Shue; Sun, Jian; Xiao, Yuan; Lu, Yi; Zhang, Donna; Wong, Pak Kin.

In: Advanced Biosystems, Vol. 1, No. 1-2, 1600019, 01.02.2017.

Research output: Contribution to journalArticle

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AU - Zhang, Donna

AU - Wong, Pak Kin

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