Vascular growth factor binding kinetics to the endothelial cell basement membrane, with a kinetics-based correction for substrate binding

Clyne, Alisa Morss; Edelman, Elazer R.

doi:10.1007/s10616-009-9212-1

Cited by 10 publications

(7 citation statements)

References 38 publications

(48 reference statements)

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“…Interactions between GFs and the ECM are known to be essential for controlling GF release kinetics in vivo, which strongly modulates tissue morphogenesis 28 . While sequestration of GFs within basement membranes was previously reported to be mediated through binding to glycosaminoglycans 47 , our data demonstrate that laminin can serve this GF reservoir function as well. In addition, the laminin diversity in different tissue ECMs and the different GF-binding profiles could be associated with regulation of GF contents and functions in specific tissues.…”

Section: Discussionsupporting

confidence: 46%

Laminin heparin-binding peptides bind to several growth factors and enhance diabetic wound healing

et al. 2018

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Laminin, as a key component of the basement membrane extracellular matrix (ECM), regulates tissue morphogenesis. Here, we show that multiple laminin isoforms promiscuously bind to growth factors (GFs) with high affinity, through their heparin-binding domains (HBDs) located in the α chain laminin-type G (LG) domains. These domains also bind to syndecan cell-surface receptors, promoting attachment of fibroblasts and endothelial cells. We explore the application of these multifunctional laminin HBDs in wound healing in the type-2 diabetic mouse. We demonstrate that covalent incorporation of laminin HBDs into fibrin matrices improves retention of GFs and significantly enhances the efficacy of vascular endothelial cell growth factor (VEGF-A165) and platelet-derived growth factor (PDGF-BB) in promoting wound healing in vivo, under conditions where the GFs alone in fibrin are inefficacious. This laminin HBD peptide may be clinically useful by improving biomaterial matrices as both GF reservoirs and cell scaffolds, leading to effective tissue regeneration.

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Section: Discussionsupporting

confidence: 46%

Laminin heparin-binding peptides bind to several growth factors and enhance diabetic wound healing

et al. 2018

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“…Interactions between GFs and the ECM are known to be essential for controlling GFs release kinetics in vivo, which strongly modulates tissue morphogenesis 26 . While sequestration of GFs within basement membranes was previously reported to be mediated through binding to glycosaminoglycans 35 , our data demonstrates that laminin can serve this GF reservoir function as well.…”

Section: Discussionsupporting

confidence: 42%

Laminin heparin-binding peptides promiscuously bind growth factors and enhance diabetic wound healing

Ishihara

Fukunaga

Briquez

et al. 2018

Preprint

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Laminin, as a key component of the basement membrane extracellular matrix (ECM), regulates tissue morphogenesis. We show that multiple laminin isoforms promiscuously bind to growth factors (GFs) with high affinity, through their heparin binding domains (HBDs) located in the a chain LG domains.Interestingly, these domains also bind to syndecan cell-surface receptors, promoting attachment of fibroblasts and endothelial cells. We next explore application of these multifunctional laminin HBDs in skin healing in the type 2 diabetic mouse. We demonstrate that covalent incorporation of laminin HBDs into fibrin matrix enables the slow-release of GFs. Incorporation of the α3

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“…Initial FGFR and HSPG surface concentrations were set to experimentally determined values of 2.5 × 10 3 receptors/cell (4.15 × 10 −12 mol/m 2 ) and 1.3 × 10 5 receptors/cell (2.16 × 10 −10 mol/m 2 ), respectively, for cardiac microvascular endothelial cells 32,33 . Basement membrane HSPG surface concentration was defined as the experimentally determined value (4.48 × 10 −8 mol/m 2 ) 16,34 . Initial cell-surface FGF2 was 0, while initial basement membrane FGF2 concentration was 1.74 × 10 −14 mol/m 2 (volumetric FGF2 concentration of 0.35 pmol/cm 3 converted to mol/m 2 using basement membrane thickness of 50 nm) 32 .…”

Section: Fgf2 Model Developmentmentioning

confidence: 99%

Fibroblast Growth Factor-2 Binding to Heparan Sulfate Proteoglycans Varies with Shear Stress in Flow-Adapted Cells

et al. 2019

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Fibroblast Growth Factor 2 (FGF2), an important regulator of angiogenesis, binds to endothelial cell (EC) surface fibroblast growth factor receptors (FGFR) and heparan sulfate proteoglycans (HSPG). FGF2 binding kinetics have been predominantly studied in static culture; however, the endothelium is constantly exposed to flow which may affect FGF2 binding. We therefore used experimental and computational techniques to study how EC FGF2 binding changes in flow. ECs adapted to 24 hours of flow demonstrated biphasic FGF2-HSPG binding, with FGF2-HSPG complexes increasing up to 20 dynes/cm 2 shear stress and then decreasing at higher shear stresses. To understand how adaptive EC surface remodeling in response to shear stress may affect FGF2 binding to FGFR and HSPG, we implemented a computational model to predict the relative effects of flow-induced surface receptor changes. We then fit the computational model to the experimental data using relationships between HSPG availability and FGF2-HSPG dissociation and flow that were developed from a basement membrane study, as well as including HSPG production. These studies suggest that FGF2 binding kinetics are altered in flow-adapted ECs due to changes in cell surface receptor quantity, availability, and binding kinetics, which may affect cell growth factor response.

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Vascular growth factor binding kinetics to the endothelial cell basement membrane, with a kinetics-based correction for substrate binding

Cited by 10 publications

References 38 publications

Laminin heparin-binding peptides bind to several growth factors and enhance diabetic wound healing

Laminin heparin-binding peptides bind to several growth factors and enhance diabetic wound healing

Laminin heparin-binding peptides promiscuously bind growth factors and enhance diabetic wound healing

Fibroblast Growth Factor-2 Binding to Heparan Sulfate Proteoglycans Varies with Shear Stress in Flow-Adapted Cells

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