Engineering cell motility via substrate incorporation of poly(ethylene glycol)

This study examined the modulation of cell migratory responsiveness to protein-adsorbed poly(ethylene glycol) (PEG) variant copolymers. To this end, fibronectin was adsorbed to equivalent levels on copolymers based on a family of tyrosine/PEG derived polycarbonates. Atomic force microscopy (AFM) revealed unique protein distributions for each copolymer system, indicating that although equal amounts of ligand are presented, the concentration of PEG in the underlying substrate can effect the adsorbed ligand. Consequently, quantitation of fibronectin RGD-binding sites on the protein-adsorbed copolymers revealed that cell-binding sites were maximized at intermediate concentrations of PEG. Our migration studies demonstrated that increasing PEG in the copolymer increased cell speed monotonically up to an intermediate PEG level where a maximum speed was reached. After incubating cells on ligand adsorbed copolymers, higher PEG levels elicited equivalent number of cell-binding sites relative to those on intermediate levels of PEG. Integrin inhibition studies showed that α₅β₁ was critical in modulating the number of RGD sites. Our AFM data suggests that rearrangement at higher PEG levels was facilitated by electrostatic repulsion, effecting fibronectin slippage at the polymer surface as well as conformational rearrangement revealing addition al RGD binding sites. Overall, we report on the finding that cell migratory responsiveness to a given ligand concentration can be further manipulated via systematic ligand changes due to the substrate PEG composition.