Nanoscale clustering of RGD peptides at surfaces using comb polymers. 1. Synthesis and characterization of comb thin films

Theoretical and experimental studies were conducted to elucidate the struct ure and properties of amphiphilic comb polymer thin films presenting nanosc ale clusters of Arg-Gly-Asp (RGD) peptides for control of cell adhesion on biomaterials. Combs comprised of a poly(methyl methacrylate) backbone and s hort poly(ethylene oxide) side chains were synthesized, and peptides were t ethered to the side chain ends to create nanoscale peptide clusters. In thi n films, comb polymers containing greater than or equal to 30 wt % six to n ine unit PEO side chains completely resisted adhesion of a model fibroblast cell line in the presence of 7.5% serum over 24 h. These same polymers mod ified with RGD peptides elicited tunable cell adhesion when mixed with unmo dified combs in varying proportion. A self-consistent field lattice model o f the interface between comb polymer films and water predicts an organizati on of the top molecular layer of comb polymer with the backbone oriented pa rallel to the interface in quasi-two-dimensional confinement and hydrophili c side chains extended in a brushlike layer into solution. This picture of a quasi-2D configuration is consistent with the observed surface properties of comb films in water as well as measurements of the RGD cluster density on mixed comb surfaces using fluorescent nanosphere labeling of ligand clus ters.