ArticleIntegrative biology : quantitative biosciences from nano to macro2011
VEGF internalization is not required for VEGFR-2 phosphorylation in bioengineered surfaces with covalently linked VEGF.
Article in Integrative biology : quantitative biosciences from nano to macro, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
24 citing papers in PubMed, 53 citations in OpenAlex.
- Delivery of Angiogenic Therapy from Flowable Hyaluronic Acid Porous Scaffolds Results in Functional Improvement without Anti-Inflammatory Agents.Advanced functional materials · 2025Article
- Sequential sequestrations increase the incorporation and retention of multiple growth factors in mineralized collagen scaffolds.RSC advances · 2020Article
- Poly(ethylene glycol)-crosslinked gelatin hydrogel substrates with conjugated bioactive peptides influence endothelial cell behavior.Biomaterials · 2019Article
- Context-dependent regulation of receptor tyrosine kinases: Insights from systems biology approaches.Wiley interdisciplinary reviews. Systems biology and medicine · 2019Review
- Cancer-derived small extracellular vesicles promote angiogenesis by heparin-bound, bevacizumab-insensitive VEGF, independent of vesicle uptake.Communications biology · 2019Article
- Dual-function injectable angiogenic biomaterial for the repair of brain tissue following stroke.Nature materials · 2018Article
- Engineering Approaches to Study Cellular Decision Making.Annual review of biomedical engineering · 2018Review
- Synthetic microparticles conjugated with VEGFNature communications · 2017Article
- Proangiogenic Activity of Endometrial Epithelial and Stromal Cells in Response to Estradiol in Gelatin Hydrogels.Advanced biosystems · 2017Article
- Dynasore impairs VEGFR2 signalling in an endocytosis-independent manner.Scientific reports · 2017Article
- A computational analysis of in vivo VEGFR activation by multiple co-expressed ligands.PLoS computational biology · 2017Article
- Engineering A11 Minibody-Conjugated, Polypeptide-Based Gold Nanoshells for Prostate Stem Cell Antigen (PSCA)-Targeted Photothermal Therapy.SLAS technology · 2017Article
- RhoGTPase stimulation is associated with strontium chloride treatment to counter simulated microgravity-induced changes in multipotent cell commitment.NPJ microgravity · 2017Article
- Cell-Demanded VEGF Release via Nanocapsules Elicits Different Receptor Activation Dynamics and Enhanced Angiogenesis.Annals of biomedical engineering · 2016Article
- The use of covalently immobilized stem cell factor to selectively affect hematopoietic stem cell activity within a gelatin hydrogel.Biomaterials · 2015Article
- Site-Specific Phosphorylation of VEGFR2 Is Mediated by Receptor Trafficking: Insights from a Computational Model.PLoS computational biology · 2015Article
- Design of growth factor sequestering biomaterials.Chemical communications (Cambridge, England) · 2014Review
- Rac1 GTPase silencing counteracts microgravity-induced effects on osteoblastic cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- HYDROGEL-BASED NANOCOMPOSITES OF THERAPEUTIC PROTEINS FOR TISSUE REPAIR.Current opinion in chemical engineering · 2014Article
- Extracellular regulation of VEGF: isoforms, proteolysis, and vascular patterning.Cytokine & growth factor reviews · 2014Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Vascular endothelial growth factor (VEGF) is known to activate proliferation, migration, and survival pathways in endothelial cells through phosphorylation of VEGF receptor-2 (VEGFR-2). VEGF has been incorporated into biomaterials through encapsulation, electrostatic sequestration, and covalent attachment, but the effect of these immobilization strategies on VEGF signaling has not been thoroughly investigated. Further, although growth factor internalization along with the receptor generally occurs in a physiological setting, whether this internalization is needed for receptor phosphorylation is not entirely clear. Here we show that VEGF covalently bound through a modified heparin molecule elicits an extended response of pVEGFR-2 in human umbilical vein endothelial cells (HUVECs) and that the covalent linkage reduces internalization of the growth factor during receptor endocytosis. Optical tweezer measurements show that the rupture force required to disrupt the heparin-VEGF-VEGFR-2 interaction increases from 3-8 pN to 6-12 pN when a covalent bond is introduced between VEGF and heparin. Importantly, by covalently binding VEGF to a heparin substrate, the stability (half-life) of VEGF is extended over three-fold. Here, mathematical models support the biological conclusions, further suggesting that VEGF internalization is significantly reduced when covalently bound, and indicating that VEGF is available for repeated phosphorylation events.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.