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

Authors
Sterner, Eric
Meli, Luciana
Kwon, Seok Joon
Dordick, Jonathan S.
Linhardt, Robert J.
ORCID
https://orcid.org/0000-0003-2219-5833
No Thumbnail Available
Other Contributors
Issue Date
2013-12-17
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Degree
Terms of Use
In Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). https://rightsstatements.org/page/InC/1.0/
Full Citation
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.
Abstract
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.
Description
Biochemistry, 52, 9009−9019
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Biochemistry
https://harc.rpi.edu/
Access
https://login.libproxy.rpi.edu/login?url=https://doi.org/10.1021/bi401284r