Noncovalent Cell Surface Engineering with Cationic Graft Copolymers

Chemical approaches to cell surface engineering have emerged as powerful tools for resurfacing the molecular landscape of cells and tissues. Here we report a new strategy for re-engineering cell surfaces through electrostatic adsorption of appropriately structured and functionalized poly(l-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) copolymers to cellular interfaces. Grafting of methoxy terminated tetra(ethylene glycol) chains to PLL abrogated polycation cytotoxicity in a charge density and PEG dependent manner, and copolymers structured with a unique balance of grafted PEG chains and free lysine monomers adsorbed to cell surfaces without compromising viability. Structurally analogous PLL-g-PEG copolymers bearing terminally functionalized PEG grafts were used as 'cell surface active' polymeric carriers for biotin, hydrazide, and azide moieties, which selectively captured streptavidin-, aldehyde-, and cyclooctyne-labeled probes, respectively, on cell surfaces. This strategy opens new opportunities in cell surface engineering, including generation of unique cell surface motifs, rapid and combinatorial surface modification, and use of biologically complex solvents. Tailored PLL-g-PEG copolymers offer a promising and enabling tool for bio/chemically remodeling cells and tissues with broad potential in biomedical and biotechnological applications.