Thermosensitive “Smart” Surfaces for Biorecognition Based Cell Adhesion and Controlled Detachment

The biorecognition‐based control of attachment/detachment of MCF‐7 cancer cells from polymer‐coated surfaces is demonstrated. A glass surface is coated with a thermoresponsive statistical copolymer of poly(N‐isopropylacrylamide‐co‐acrylamide) [p(NIPAm‐co‐Am)], which is end‐capped with the Gly‐Arg‐Gly‐Asp‐Ser (GRGDS) peptide, and the hydrophilic polymer poly(ethylene glycol) (PEG). Below the lower critical solution temperature (LCST) of p(NIPAm‐co‐Am) (38 °C), the copolymers are in the extended conformation, allowing for accessibility of the GRGDS peptides to membrane‐associated integrins thus enabling cell attachment. Above the LCST, the p(NIPAm‐co‐Am) polymers collapse into globular conformations, resulting in the shielding of the GRGDS peptides into the PEG brush with consequent inaccessibility to cell‐surface integrins, causing cell detachment. The surface coating is carried out by a multi‐step procedure that included: glass surface amination with 3‐aminopropyltriethoxysilane; reaction of mPEG5kDa‐N‐hydroxysuccinimide (NHS) and p(NIPam‐co‐Am)15.1kDa‐bis‐NHS with the surface aminopropyl groups and conjugation of GRGDS to the carboxylic acid termini of p(NIPam‐co‐Am)15.1kDa‐COOH. A range of spectrophotometric, surface, and microscopy assays confirmed the identity of the polymer‐coated substrates. Competition studies prove that MCF‐7 cancer cells are attached via peptide recognition at the coated surfaces according to the mPEG5kDa/p(NIPam‐co‐Am)15.1kDa‐GRGDS molar ratio. These data suggest the system can be exploited to modulate cell integrin/GRGDS binding for controlled cell capture and release.