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

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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.

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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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Acknowledgments

This work was supported by National Institutes of Health Grant R01 NS40394, New Jersey Commission on Spinal Cord Research Grant 04-3034 SCR-E-O, and funds from Donaldson Co., Inc. to S.M.

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Authors and Affiliations

  1. Department of Biology, Medgar Evers College of the City University of New York, Brooklyn, NY, 11225, USA

    Alam Nur-E-Kamal

  2. Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ, 08854, USA

    Ijaz Ahmed, Jabeen Kamal, Ashwin N. Babu & Sally Meiners

  3. NanoCulture, LLC, 117 Bedford Court, Piscataway, NJ, 08854, USA

    Melvin Schindler

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  1. Alam Nur-E-Kamal
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  2. Ijaz Ahmed
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Correspondence to Alam Nur-E-Kamal.

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Nur-E-Kamal, A., Ahmed, I., Kamal, J. et al. Covalently attached FGF-2 to three-dimensional polyamide nanofibrillar surfaces demonstrates enhanced biological stability and activity. Mol Cell Biochem 309, 157–166 (2008). https://doi.org/10.1007/s11010-007-9654-8

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