Protein adsorption on charge regulating silica nanoparticles: Understanding the effects of pH, ionic strength, and curvature.

Abstract

Protein adsorption onto silica nanoparticles is governed by a complex interplay between electrostatics, acid-base chemistry, and short-range interactions. In this work, we develop a molecular theory that explicitly incorporates charge regulation of both silica silanols and protein titratable residues, together with residue-specific short-range interactions, to investigate the adsorption of lysozyme (basic protein) and β-lactoglobulin (acidic protein) onto spherical silica nanoparticles. This framework predicts systematic trends in protein adsorption as a function of pH, ionic strength, and nanoparticle size. Our results reveal that protein adsorption on silica nanoparticles arises from a separation of length scales: short-range interactions control the contact layer, while long-range electrostatics govern repulsive barriers that produce a protein-depleted region beyond the adsorbed layer due to protein-protein repulsions. Curvature modulates adsorption exclusively through electrostatics, enhancing surface charge, weakening these repulsive barriers, and attenuating secondary adsorption layers, while leaving short-range binding unchanged. Competitive adsorption from equimolar binary mixtures reveals a pH-controlled switch in surface selectivity between β-lactoglobulin and lysozyme, which shifts with salt concentration. Overall, this framework provides a predictive basis for tuning protein-nanoparticle interactions across solution conditions and particle sizes, offering a foundation for designing nanomaterials with controlled interfacial behavior.