Poly(ethylene glycol)-Based Surfactant Reduces the Conformational Change of Adsorbed Proteins on Nanoparticles

[Image: see text] When in contact with a biological medium, the surfaces of nanoparticles are usually covered by proteins. In this regard, it was found that poly(ethylene glycol) (PEG) promotes the “stealth effect”. This implies a reduction of unspecific protein adsorption and cellular uptake. Although information about the PEG–protein interaction was reported, more accurate and sophisticated structure and dynamics analyses are needed to understand the interaction processes in detail. This work studies the PEG–protein interaction using model nanoparticles stabilized either by the PEG-based surfactant Lutensol AT50 or sodium dodecyl sulfate. The interaction with human serum albumin was studied using neutron scattering techniques. The parameters obtained by small-angle neutron scattering yielded information about the adsorbed protein layer thickness. Protein structure changes were detected via differential scanning fluorimetry and elastic neutron scattering. This combination gives a better insight into the PEG–protein interaction, contributing to the design of nanomaterials for medical applications.