Poly(vinyl sulfonate) Facilitates bFGF-Induced Cell Proliferation

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Cell Biology

Background:

• Heparin, a sulfated polysaccharide, has diverse biological functions but suffers from batch-to-batch variability.
• Developing heparin biomimetics is crucial for consistent therapeutic and research applications.
• Fibroblast Growth Factor Receptors (FGFRs) play key roles in cell signaling and proliferation.

Purpose of the Study:

• To identify polymeric heparin mimetics with consistent biological functions.
• To evaluate poly(vinyl sulfonate) (pVS) as a potential heparin replacement.
• To investigate the mechanism of pVS in enhancing growth factor binding and receptor activation.

Main Methods:

• Development of a cell-based screening assay using cells expressing FGFRs.
• Screening of various sulfated and sulfonated polymers.
• Confirmation of binding enhancement using ELISA assays.
• Synthesis of different molecular weights of pVS via RAFT polymerization.

Main Results:

• Poly(vinyl sulfonate) (pVS) demonstrated the strongest heparin-mimicking activity by enhancing basic fibroblast growth factor (bFGF) binding to FGFRs.
• pVS facilitated FGFR dimerization, leading to cell proliferation in FGFR-expressing cells, with no observed size dependence.
• ELISA assays confirmed pVS's ability to enhance bFGF-FGFR interactions.
• pVS exhibited no cytotoxicity to fibroblast cells at concentrations up to 1 mg/mL.

Conclusions:

• Poly(vinyl sulfonate) (pVS) is a potent heparin mimetic with comparable efficacy to heparin in enhancing FGFR-mediated signaling.
• pVS represents a promising, non-cytotoxic alternative to heparin for applications requiring consistent performance.
• Further exploration of pVS as a heparin replacement is warranted based on its demonstrated biological activity and safety profile.