Measurements of interbilayer forces and protein adsorption on uncharged lipid bilayers displaying poly(ethylene glycol) chains

Poly(ethylene glycol) (PEG)-stabilized liposomes were recently shown to exh ibit differences in cell uptake that were linked to the liposome charge. To determine the differences and similarities between charged and uncharged P EG-decorated liposomes, we directly measured the forces between two support ed, neutral bilayers with terminally grafted PEG chains. The measurements w ere performed with the surface force apparatus. The force profiles were sim ilar to those measured with negatively charged PEG conjugates of 1,2-distea royl-sn-glycero-3-phosphatidyl ethanolamine (DSPE), except that they lacked the longer ranged electrostatic repulsion observed with the charged compou nd. Theories for simple polymers describe the forces between end-grafted po lymer chains on neutral bilayers. The force measurements were complemented by surface plasmon resonance studies of protein adsorption onto these layer s. The lack of electrostatic forces reduced the adsorption of positively ch arged proteins and enhanced the adsorption of negatively charged ones. The absence of charge also allowed us to determine how membrane charge and the polymer grafting density independently affect protein adsorption on the coa ted membranes. Such studies suggest the physical basis of the different int eractions of charged and uncharged liposomes with proteins and cells.