Redox-Triggered Control of Cell Adhesion and Deadhesion on Poly(lysine)- g -poly(ethylene oxide) Adlayers
Résumé
Spontaneous adsorption of poly(lysine)-g-poly(ethyleneglycol) comb-like copolymers (PLL-g-PEG) is a versatile mean to coat substrates with polymer layers that resist cell adhesion. We prepared redox cleavable PLL-g-PEG to switch adhesion on demand. Redox sensitivity was obtained by introducing disulfide linkers between the PLL backbone and PEG strands. This modification was done alone or in combination with an azide-end on the PEG strands that enabled in situ conjugations of adhesion peptides or fluorescent labels (by simple application of commercially available molecules for copper-free click chemistry compatible with cell survival). To balance the functional (adhesion-promoting) vs cell-repellent copolymers, mixed layers of adjusted compositions were obtained by coadsorption from mixed solutions of the cleavable copolymer with non-cleavable and repellant PLL-g-PEG. The deposition of copolymers and quantitative cleavage as triggered by reductive conditions (application of solutions of tris(carboxyethyl)phosphine, dithiothreitol or gluthatione) were characterized by QCM-D, XPS, and fluorescence microscopy. In cell culture conditions, redox-triggered cleavage was obtained by non toxic application of TCEP for a few minutes, enabling either to release cell attachment points (i.e. cleavage of RGD-presenting areas) or to "open" non-specific adherent areas (i.e. transition from PEG-presenting areas to adherent PLL-like coatings).
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