Bimodal polymer mushrooms: compressive forces and specificity toward receptor surfaces

End-grafted poly(ethylene glycol) (or PEG) polymer chains are used to extend the in vivo circulation time of targeted liposomes and nanoparticles; however, the most efficacious structure for also imparting high target specificity remains unknown. Using the surface force apparatus, we have measured the specific and nonspecific forces between bimodal mixtures of grafted polymer mushrooms and model receptor surfaces. Specifically, supported lipid membranes anchoring 2000 or 5000 Da PEG with a controlled fraction of PEG(2000) bearing biotin ligands were compressed against opposing streptavidin surfaces. The presence of the longer 5000 Da chain increased the steric repulsion of the bimodal mushroom layer and thus decreased the net adhesive force when shorter chains were ligated. However, the 5000 Da chain did not detectably alter the distance where ligand-receptor binding occurs and adhesion begins. This latter result is in good agreement with theoretical predictions based on summing the repulsive steric and attractive bridging forces. Further, all ligated structures adhered to receptors under both static and dynamic fluid flow conditions. The dynamic movement of the flexible PEG tethers permitted ligand-receptor bonds to form far beyond the equilibrium edge of the bimodal mushroom layer. This work demonstrates that liposome targeting should be enhanced by grafting ligands to liposomes with a tether that has a contour length longer than the equilibrium height of the bimodal mushroom layer.