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

Abstract

Protein 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 important role in 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, the results show that small proteins behaved as typical model proteins, forming homogeneous 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 into proteomics and toxicological studies.

Polymer Topology Determines the Formation of Protein Corona on Core–Shell Nanoparticles

“…The results are superior to those from previous ITC measurements on PEG- and PAOXA-grafted NPs, which display colloidal stability in biofluids and reduced phagocytosis by macrophages. ,, HSA is the by far most abundant and one of the most sticky proteins in human blood serum, which makes it likely that this stealth property extends to most proteins. However, ITC and other investigations have shown that protein physicochemical properties, including size, flexibility, and surface charge, influence their adsorption on nanoparticles. ,, Future inquiries should address this point by rigorous testing with proteins and biomolecules with diverse biophysical properties.…”

“…However, ITC and other investigations have shown that protein physicochemical properties, including size, flexibility, and surface charge, influence their adsorption on nanoparticles. 17 , 47 , 48 Future inquiries should address this point by rigorous testing with proteins and biomolecules with diverse biophysical properties.…”

Relationships between RNA topology and nucleocapsid structure in a model icosahedral virus

“…This can lead to underestimations of the actual stoichiometry of the reaction. Such a bias was observed for proteins interacting on hydroxyapatite (68) and silica surfaces (69). However, despite this discrepancy, a relative comparison could be done and similar trends between and up could be observed.…”

Optimization of Nanohybrid Biosensors Based on Electro-Crosslinked Tannic Acid Capped Nanoparticles/Enzyme

“…In this case, the highest enzymatic activity was obtained with an optimum gold NPs size of 10 nm [ 12 ]. Two antagonist effects are often competing: (i) large NPs adsorb more enzymes than small ones leading to higher activity per NPs [ 13 , 14 ], and (ii) small NPs seem to impact the activity of the adsorbed enzymes less than the large ones [ 12 , 15 , 16 ]. Thus, an optimal NP size is eventually found at a given enzyme and NPs concentrations.…”

“…Thus, an optimal NP size is eventually found at a given enzyme and NPs concentrations. Moreover, the protein size regarding NP size was recently found to be also crucial [ 13 ]. As a general trend, the activity of large enzymes (>100 kDa) increases with the NPs size [ 15 , 16 , 17 ] whereas the activity of small enzymes (<50 kDa) decreases with the increase of NPs size [ 11 , 18 , 19 ].…”