Heterogeneity in VEGF Receptor-2 Mobility and Organization on the Endothelial Cell Surface Leads to Diverse Models of Activation by VEGF

Bruno da Rocha-Azevedo, Sungsoo Lee, Aparajita Dasgupta, Anthony R. Vega, Luciana R. de Oliveira, Tae Kim, Mark Kittisopikul, Zachariah A. Malik, Khuloud Jaqaman

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The dynamic nanoscale organization of cell surface receptors plays an important role in signaling. We determine this organization and its relation to activation of VEGF receptor-2 (VEGFR-2), a critical receptor tyrosine kinase in endothelial cells (ECs), by combining single-molecule imaging of endogenous VEGFR-2 in live ECs with multiscale computational analysis. We find that surface VEGFR-2 can be mobile or exhibit restricted mobility and be monomeric or non-monomeric, with a complex interplay between the two. This basal heterogeneity results in heterogeneity in the sequence of steps leading to VEGFR-2 activation by VEGF. Specifically, we find that VEGF can bind to monomeric and non-monomeric VEGFR-2 and that, when binding to monomeric VEGFR-2, its effect on dimerization depends on the mobility of VEGFR-2. Our study highlights the dynamic and heterogeneous nature of cell surface receptor organization and the need for multiscale, single-molecule-based analysis to determine its relationship to receptor activation and signaling.

Original languageEnglish (US)
Article number108187
JournalCell Reports
Volume32
Issue number13
DOIs
StatePublished - Sep 29 2020

Keywords

  • VEGFR
  • angiogenesis
  • computational analysis
  • multi-scale
  • nanoscale
  • particle tracking
  • quantitative microscopy
  • single-molecule imaging
  • spatiotemporal
  • stochastic

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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