We report interactions between adsorbed copolymers of poly(ethylene glycol) (PEG) in the presence of two abundant blood proteins, serum albumin and an immunoglobulin G, up to physiological blood concentrations. We directly and nonintrusively measure interactions between PEG triblock copolymers (PEG–PPO–PEG) adsorbed to hydrophobic colloids and surfaces using Total Internal Reflection Microscopy, which provides kT- and nanometer-scale resolution of interaction potentials (energy vs separation). In the absence of protein, adsorbed PEG copolymer repulsion is consistent with dimensions and architectures of PEG brushes on both colloids and surfaces. In the presence of proteins, we observe concentration dependent depletion attraction and no change to brush repulsion, indicating protein exclusion from PEG brushes. Because positive and negative protein adsorption are mutually exclusive, our observations of concentration dependent depletion attraction with no change to brush repulsion unambiguously indicate the absence of protein coronas at physiological protein concentrations. These findings demonstrate a direct sensitive approach to determine interactions between proteins and particle/surface coatings important to diverse biotechnology applications.
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