Molecular and Cellular Biochemistry

, Volume 309, Issue 1–2, pp 157–166 | Cite as

Covalently attached FGF-2 to three-dimensional polyamide nanofibrillar surfaces demonstrates enhanced biological stability and activity

  • Alam Nur-E-Kamal
  • Ijaz Ahmed
  • Jabeen Kamal
  • Ashwin N. Babu
  • Melvin Schindler
  • Sally Meiners
Article

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°C or 4°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.

Keywords

Fibroblast growth factor Covalent linkage Stability Three-dimensional nanofibrillar surfaces Signaling Proliferation Differentiation Embryonic stem cells 

Abbreviations

FGF-2

Fibroblast growth factor 2

SDPD

Sulfosuccinimidyl 6-[3’(2-pyridyldithio)-propionamido] Hexanoate)

FGFR

Fibroblast growth factor receptor

ECM

Extracellular matrix

BM

Basement membrane

ERK

Extracellular signal-regulated kinase

JNK

c-Jun amino-terminal kinase

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Copyright information

© Springer Science+Business Media, LLC. 2007

Authors and Affiliations

  • Alam Nur-E-Kamal
    • 1
  • Ijaz Ahmed
    • 2
  • Jabeen Kamal
    • 2
  • Ashwin N. Babu
    • 2
  • Melvin Schindler
    • 3
  • Sally Meiners
    • 2
  1. 1.Department of BiologyMedgar Evers College of the City University of New YorkBrooklynUSA
  2. 2.Department of PharmacologyUMDNJ-Robert Wood Johnson Medical SchoolPiscatawayUSA
  3. 3.NanoCulture, LLCPiscatawayUSA

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