The effect of extensible PEG tethers on shielding between grafted thermo-responsive polymer chains and integrin-RGD binding.
The affinity control of integrin-RGD (Arg-Gly-Asp) binding by a thermal "on-off" switch has been achieved using newly designed surfaces presenting grafted temperature-responsive poly(N-isopropylacrylamide-co-2-carboxyisopropylacrylamide) copolymers functionalized with synthetic peptides. The prepared surface was designed to expose the tethered peptides available for cell binding at active "on" state above the lower critical solution temperature (LCST). The fully extended chains, on the other hand, masked the peptides completely and the cells started to detach from the surfaces at inactive "off" sate below the LCST. This paper elucidates the shielding effect of the grafted polymer chains on the dissociation of integrin-RGD binding below the LCST. To assess the ability of the polymer-shielding, extensible poly(ethylene glycol) (PEG) tethers were introduced between peptides and the grafted polymers. PEG chains allow peptides to be tethered to surfaces via functional PEG end-groups, leading to active "on" state even below the LCST. The time required to release cells from the surface was found to be longer when peptides were coupled to an extensible tether ends, suggesting that the surfaces can engender cell attachment through adhesive moieties covalently bound to the free ends of PEG chains. These results indicate that architectural changes on the nanometer length scale are crucial for controlling integrin-RGD binding and one of the main factors causing cell detachment is the shielding effect of the grafted polymer chains.
Ebara
Mitsuhiro
M
Department of Applied Chemistry, Waseda University, 3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555, Japan.
Yamato
Masayuki
M
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Aoyagi
Takao
T
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Kikuchi
Akihiko
A
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Sakai
Kiyotaka
K
Department of Applied Chemistry, Waseda University, 3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555, Japan.
Okano
Teruo
T
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
D000818:Animals; D002417:Cattle; D002448:Cell Adhesion; D016023:Integrins / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*
D016023:Integrins; D009842:Oligopeptides; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid