title: Covalently attached FGF-2 to three-dimensional polyamide nanofibrillar surfaces demonstrates enhanced biological stability and activity.
abstract: Activation of fibroblast growth factor receptors (FGFRs) requires the formation of a ternary complex between fibroblast growth factors (FGFs), FGFRs, and heparan sulfate proteoglycans, which are all located on the cell surface and the basement membrane (BM)/extracellular matrix (ECM). Heparan sulfate proteoglycans appear to stabilize FGFs by inhibiting the rapid degradation of FGFs normally observed in solution. Because of the pivotal role of FGFs in proliferative and developmental pathways, a number of recent studies have attempted to engineer microenvironments to stabilize growth factors for use in applications in tissue culture and regenerative medicine. In this communication, we demonstrate that covalent linkage of FGF-2 to nanofibrillar surfaces (defined as covalently bound FGF-2) composed of a network of polyamide nanofibers resulted in the maintenance of the biological efficacy of FGF-2 when stored dry for at least 6 months at 25 degrees C or 4 degrees C. Moreover, covalently bound FGF-2 was more potent than FGF-2 in solution when measured in cellular assays of proliferation and viability using a variety of cell types. Covalently bound FGF-2 also strongly activated FGFR, extracellular signal-regulated kinase (ERK1/2), and c-fos. Hence cell-signaling molecules can be incorporated into a synthetic nanofibrillar surface, providing a novel means to enhance their stability and biological activity.
authors.affiliation: Department of Biology, Medgar Evers College of the City University of New York, Brooklyn, NY 11225, USA. alam@mec.cuny.edu
authors.forename: Alam
authors.initials: A
authors.lastname: Nur-E-Kamal
authors.forename: Ijaz
authors.initials: I
authors.lastname: Ahmed
authors.forename: Jabeen
authors.initials: J
authors.lastname: Kamal
authors.forename: Ashwin N
authors.initials: AN
authors.lastname: Babu
authors.forename: Melvin
authors.initials: M
authors.lastname: Schindler
authors.forename: Sally
authors.initials: S
authors.lastname: Meiners
mesh_terms: D000327:Adsorption / Q000187:drug effects; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D049329:Nanostructures; D009757:Nylons / Q000378:metabolism*; D051381:Rats; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D003432:Cross-Linking Reagents; D009757:Nylons; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D006493:Heparin