A COMPUTATIONAL MODEL OF FIBROBLAST GROWTH FACTOR-2 BINDING TO ISOLATED AND INTACT CELL SURFACE RECEPTORS: EFFECTS OF FIBROBLAST GROWTH FACTOR-2 CONCENTRATION, FLOW AND DELIVERY MODE

摘要

Fibroblast growth factor-2 (FGF2) plays an important role in both healthy vascular cell functions and pathogenesis in cancer, atherosclerosis and reduced perfusion in diabetes (1-4). FGF2 therapy and targeted drug delivery have great potential in the treatment of such diseases, but have had little clinical success. FGF2 binding kinetics to heparan sulfate proteoglycan (HSPG) and fibroblast growth factor receptors (FGFR) have been largely studied under static conditions (5), however FGF2 binding to endothelial cells occurs physiologically under fluid flow conditions. Understanding complex FGF2 binding kinetics would enable the development of new anti-and pro-angiogenic therapeutics. We developed a computational model of FGF2 binding to FGFR and HSPG with flow to investigate the effect of fluid flow and FGF2 delivery mode on FGF2 binding to isolated or combined binding sites.