The Importance of Protein Size in Protein-Nanoparticle Interactions: From Protein Corona to Colloidal Self-Assembly

International audienceProtein adsorption on nanoparticles is an important field of study, particularly with regard to nanomedicine and nanotoxicology. Many factors can influence the composition and structure of the layer(s) of adsorbed proteins, the so-called “protein corona”. However, the role of protein size has not been specifically investigated, although some evidence has indicated its potential large role for corona composition and structure. To assess the role of protein size, we studied the interactions of hemoproteins (spanning a large size range) with monodisperse silica nanoparticles. We combined various techniques — adsorption isotherms, isothermal titration calorimetry, circular dichroism, and transmission electron cryomicroscopy — to address this issue. Overall, results show that small proteins behaved as typical model proteins, forming homogenous monolayers on the nanoparticle surface (protein corona). Their adsorption is purely enthalpy-driven, with subtle structural changes. In contrast, large proteins interact with nanoparticles via entropy-driven mechanisms. Their structure is completely preserved during adsorption and any given protein can directly bind to several nanoparticles forming bridges in these newly formed protein-nanoparticle assemblies. Protein size is clearly an overlooked factor that should be integrated in proteomics and toxicological studie