title: Poly(vinyl sulfonate) Facilitates bFGF-Induced Cell Proliferation.
abstract: Heparin is a highly sulfated polysaccharide and is useful because of its diverse biological functions. However, because of batch-to-batch variability and other factors, there is significant interest in preparing biomimetics of heparin. To identify polymeric heparin mimetics, a cell-based screening assay was developed in cells that express fibroblast growth factor receptors (FGFRs) but not heparan sulfate proteoglycans. Various sulfated and sulfonated polymers were screened, and poly(vinyl sulfonate) (pVS) was identified as the strongest heparin-mimicking polymer in its ability to enhance binding of basic fibroblast growth factor (bFGF) to FGFR. The results were confirmed by an ELISA-based receptor-binding assay. Different molecular weights of pVS polymer were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers were able to facilitate dimerization of FGFRs leading to cell proliferation in FGFR-expressing cells, and no size dependence was observed. The data showed that pVS is comparable to heparin in these assays. In addition, pVS was not cytotoxic to fibroblast cells up to at least 1 mg/mL. Together this data indicates that pVS should be explored further as a replacement for heparin.
authors.affiliation: Department of Chemistry and Biochemistry and California NanoSystems Institute, University of California, Los Angeles , 607 Charles E. Young Drive East, Los Angeles, California 90095-1569 United States.
authors.forename: Thi H
authors.initials: TH
authors.lastname: Nguyen
authors.affiliation: Department of Chemistry and Biochemistry and California NanoSystems Institute, University of California, Los Angeles , 607 Charles E. Young Drive East, Los Angeles, California 90095-1569 United States.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Paluck
authors.affiliation: Department of Chemistry and Biochemistry and California NanoSystems Institute, University of California, Los Angeles , 607 Charles E. Young Drive East, Los Angeles, California 90095-1569 United States.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McGahran
authors.affiliation: Department of Chemistry and Biochemistry and California NanoSystems Institute, University of California, Los Angeles , 607 Charles E. Young Drive East, Los Angeles, California 90095-1569 United States.
authors.forename: Heather D
authors.initials: HD
authors.lastname: Maynard
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006493:Heparin / Q000737:chemistry; D006801:Humans; D011145:Polyvinyls / Q000737:chemistry / Q000494:pharmacology; D013451:Sulfonic Acids / Q000737:chemistry / Q000494:pharmacology
chemical_list: D011145:Polyvinyls; D013451:Sulfonic Acids; D016222:Fibroblast Growth Factor 2; C008959:lyapolate; D006493:Heparin