FGF-FGFR signaling mediated through glycosaminoglycans in microtiter plate and cell-based microarray platforms

Sterner, Eric
Meli, Luciana
Kwon, Seok Joon
Dordick, Jonathan S.
Linhardt, Robert J.
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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FGF-FGFR signaling mediated through glycosaminoglycans in microtiter plate and cell-based microarray platforms, E. Sterner, L. Meli, J. S. Dordick, R. J. Linhardt, Biochemistry, 52, 9009−9019, 2013.
Fibroblast growth factor (FGF) signals cell growth through its interaction with a fibroblast growth factor receptor (FGFR) and a glycosaminoglycn (GAG) coreceptor. Here, we examine the signaling of five different FGFs (1, 2, 6, 8, and 8b) through FGFR3c. A small library of GAG and GAG-derivative coreceptors are screened to understand better the structure–activity relationship of these coreceptors on signaling. Initially, data were collected in a microtiter plate well-based cell proliferation assay. In an effort to reduce reagent requirements and improve assay throughput, a cell-based microarray platform was developed. In this cell-based microarray, FGFR3c-expressing cells were printed in alginate hydrogel droplets of ∼30 nL and incubated with FGF and GAG. Heparin was the most effective GAG coreceptor for all FGFs studied. Other GAGs, such as 2-O-desulfated heparin and chondroitin sulfate B, were also effective coreceptors. Signaling by FGF 8 and FGF 8b showed the widest tolerance for coreceptor structure. Finally, this on-chip cell-based microarray provides comparable data to a microtiter plate well-based assay, demonstrating that the coreceptor assay can be converted into a high-throughput assay.
Biochemistry, 52, 9009−9019
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Rensselaer Polytechnic Institute, Troy, NY