Specific buffer effects on the formation of BSA protein corona around amino-functionalized mesoporous silica nanoparticles

The effect of buffer species on biomolecules and biomolecule-nanoparticle interactions is a phenomenon that has been either neglected, or not understood. Here, we study the formation of a BSA protein corona (PC) around amino-functionalized mesoporous silica nanoparticles (MSN-NH₂) in the presence of different buffers (Tris, BES, cacodylate, phosphate, and citrate) at the same pH (7.15) and different concentrations (10, 50, and 100 mM). We find that BSA adsorption is buffer specific, with the adsorbed amount of BSA being 4.4 times higher in the presence of 100 mM Tris (184 ± 3 mg/g) than for 100 mM citrate (42 ± 2 mg/g). That is a considerable difference that cannot be explained by conventional theories. The results become clearer if the interaction energies between BSA and MSN-NH₂, considering the electric double layer (E_EDL) and the van der Waals (E_vdW) terms, are evaluated. The buffer specific PC derives from buffer specific zeta potentials that, for MSN-NH₂, are positive with Tris and negative with citrate buffers. A reversed sign of zeta potentials can be obtained by considering polarizability-dependent dispersion forces acting together with electrostatics to give the buffer specific outcome. These results are relevant not only to our understanding of the formation of the PC but may also apply to other bio- and nanosystems in biological media.