Nanoscale growth factor patterns by immobilization on a heparin-mimicking polymer.
In this study, electrostatic interactions between sulfonate groups of an immobilized polymer and the heparin binding domains of growth factors important in cell signaling were exploited to nanopattern the proteins. Poly(sodium 4-styrenesulfonate-co-poly(ethylene glycol) methacrylate) (pSS-co-pPEGMA) was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization using ethyl S-thiobenzoyl-2-thiopropionate as a chain transfer agent and 2,2'-azoisobutyronitrile (AIBN) as the initiator. The resulting polymer (1) was characterized by 1H NMR, GPC, FT-IR, and UV-vis and had a number average molecular weight (Mn) of 24,000 and a polydispersity index (PDI) of 1.17. The dithioester end group of 1 was reduced to the thiol, and the polymer was subsequently immobilized on a gold substrate. Binding of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) to the polymer via the heparin binding domains was then confirmed by surface plasmon resonance (SPR). The interactions were stable at physiological salt concentrations. Polymer 1 was cross-linked onto silicon wafers using an electron beam writer forming micro- and nanopatterns. Resolutions of 100 nm and arbitrary nanoscale features such as concentric circles and contiguous squares and triangles were achieved. Fluorescence microscopy confirmed that bFGF and VEGF were subsequently immobilized to the polymer micro- and nanopatterns.
Christman
Karen L
KL
Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles, California 90095-1569, USA.
Vázquez-Dorbatt
Vimary
V
Schopf
Eric
E
Kolodziej
Christopher M
CM
Li
Ronald C
RC
Broyer
Rebecca M
RM
Chen
Yong
Y
Maynard
Heather D
HD
D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry*; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry*; D055767:Immobilized Proteins / Q000737:chemistry*; D008689:Methacrylates / Q000737:chemistry; D008958:Models, Molecular; D036103:Nanotechnology; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D013451:Sulfonic Acids / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry*
D055767:Immobilized Proteins; D008689:Methacrylates; D011108:Polymers; D013451:Sulfonic Acids; D042461:Vascular Endothelial Growth Factor A; C524499:polyethylene glycol methacrylate; D016222:Fibroblast Growth Factor 2; D011092:Polyethylene Glycols; D006493:Heparin; C077114:styrenesulfonic acid polymer