SELF-ASSEMBLY AND STERIC STABILIZATION AT HETEROGENEOUS, BIOLOGICAL SURFACES USING ADSORBING BLOCK-COPOLYMERS

Background: We present the synthesis, characterization and initial str ucture-function analysis of a new class of bioactive agent that allows the application of techniques from colloid science to biological surf aces, Stable colloidal suspensions can be generated by immobilizing a dense brush of soluble polymer at the colloidal surface, creating a zo ne protected against the adhesion of approaching particles, a phenomen on termed polymeric steric stabilization. This is often accomplished f or aqueous colloidal dispersions using adsorbing block copolymers. We demonstrate that water-soluble block copolymers can be designed to ads orb onto heterogeneous biological surfaces and block cell-cell and cel l-surface adhesion, using polymer compositions and architectures that are quite different from surfactants used for stabilizing nonbiologica l colloidal dispersions, Results: Comb copolymers were synthesized hav ing polycationic backbones (poly-L-lysine, PLL), serving as the anchor for binding to the net negatively charged biological surfaces, grafte d with water-soluble polynonionic chains (polyethylene glycol, PEG), t o block biological recognition, producing PLL-graft-PEG copolymers, Sp ecific copolymers were found to sterically stabilize red blood cells f rom lectin-induced hemagglutination and fibroblasts from adhesion to f ibronectin-coated surfaces. The polymer design principles, which appea r to be unique for adsorption to heterogeneous biological surfaces, re quire the use of very high molecular weight comb copolymers, perhaps b ecause anionic sites are non-uniformly distributed on biological surfa ces, and the ability of larger copolymers to span between highly anion ic sites, Conclusions: Water-soluble copolymers were produced that can block recognition at biological surfaces, on the basis of nonspecific physicochemical phenomena rather than specific biochemical interactio ns.