Using mixed monolayer nanoparticles to probe the role of surface forces in protein corona formation

The formation of the nanoparticle-protein corona (NP-PC) plays an important role in NP-biological interactions, particularly mediating the interactions between nanoparticles and the cellular membrane, making it an active area of interdisciplinary research with applications in biosensing, drug delivery, and cancer therapeutics. Here, we present recent results concerning the role of surface forces in NP-protein corona formation. Gold NPs with a core diameter of approximately 5nm were synthesized with five distinct ligand combinations on the surface, yielding different surface charge signs and densities. The interaction of these functionalized NPs with BSA as a model protein is studied at both low and high salt (long and short Debye length.) UV-Vis absorbance spectroscopy, fluorescence titration, and dynamic light scattering are used to probe the system and binding constants are obtained assuming the protein adsorption follows a Langmuir isotherm. Langmuir-like behavior and approach to saturation are only reliably observed at low salt concentration, where Coulombic forces are expected to dominate. Curiously, however, the binding constants for moderately and highly negatively charged surfaces are close in magnitude, and considerably larger than that of the neutral NP, despite the relatively large number of negatively charged R-groups on the BSA.