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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Fibroblast Growth Factor-2 Binding to Heparan Sulfate Proteoglycans Varies with Shear Stress in Flow-Adapted Cells
Annals of biomedical engineering, Vol.47(4), pp.1078-1093
01 Apr 2019
PMID: 30689065
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Fibroblast growth factor 2 (FGF2), an important regulator of angiogenesis, binds to endothelial cell (EC) surface FGF receptors (FGFRs) and heparan sulfate proteoglycans (HSPGs). 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 h of flow demonstrated biphasic FGF2-HSPG binding, with FGF2-HSPG complexes increasing up to 20 dynes/cm 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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Details
- Title
- Fibroblast Growth Factor-2 Binding to Heparan Sulfate Proteoglycans Varies with Shear Stress in Flow-Adapted Cells
- Creators
- Jonathan Garcia - School of Biomedical Engineering, Science and Health Systems, Drexel University, 3141 Chestnut St, Philadelphia, PA, USANisha Patel - Drexel University, School of Biomedical Engineering, Science, and Health SystemsSarah Basehore - School of Biomedical Engineering, Science and Health Systems, Drexel University, 3141 Chestnut St, Philadelphia, PA, USAAlisa Morss Clyne - Mechanical Engineering and Mechanics Department, Drexel University, 3141 Chestnut St, Philadelphia, PA, USA. asm67@drexel.edu
- Publication Details
- Annals of biomedical engineering, Vol.47(4), pp.1078-1093
- Number of pages
- 16
- Grant note
- R01 HL140239 / NHLBI NIH HHS CBET-0846751 / Division of Chemical, Bioengineering, Environmental, and Transport Systems
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000461026400014
- Scopus ID
- 2-s2.0-85060815734
- Other Identifier
- 991021860787804721
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InCites Highlights
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- Web of Science research areas
- Engineering, Biomedical