Protein adsorption modes determine reversible cell attachment on poly(N-isopropyl acrylamide) brushes

Protein adsorption and reversible cell attachment are investigated as a function of the grafting density of poly(N-isopropyl acrylamide) (PNIPAM) brushes. Prior studies demonstrated that the thermally driven collapse of grafted PNIPAM above the lower critical solution temperature of 32 °C is not required for protein adsorption. Here, the dependence of reversible, protein-mediated cell adhesion on the polymer chain density, above and below the lower critical solution temperature, is reported. Above 32 °C, protein adsorption on PNIPAM brushes grafted from a non-adsorbing, oligo(ethylene oxide)-coated surface exhibits a maximum with respect to the grafting density. Few cells attach to either dilute or densely grafted PNIPAM chains, independent of whether the polymer brush collapses above 32 °C. However, both cells and proteins adsorb reversibly at intermediate chain densities. This supports a model in which the proteins, which support reversible cell attachment, adsorb by penetrating the brushes at intermediate grafting densities, under poor solvent conditions. In this scenario, reversible protein adsorption to PNIPAM brushes is determined by the thermal modulation of relative protein-segment attraction and osmotic repulsion. Reversible protein adsorption and expulsion is governed by the relative balance between temperature-dependent protein-segment attraction and osmotic repulsion.