Spontaneous protein desorption from self-assembled monolayer (SAM)-coated gold nanoparticles

When nanoparticles enter blood or other biological fluids, they tend to contact with a variety of proteins which may hamper their application and even bring adverse impacts. Such nonspecific protein binding is usually weak and proteins reach dynamic equilibrium between adsorption and desorption. Studies on the spontaneous desorption of weakly bound proteins should not only be helpful to enrich our understanding about such nonspecific interactions but also shed light on the strategy to avoid nonspecific binding of proteins. Here, we use molecular dynamics simulations to investigate the interactions of human serum albumin with the self-assembled monolayer (SAM)-coated gold(111) surface, a typical facet of various gold nanoparticles. The response of the protein interfacial behavior to solution pH, especially the spontaneous desorption, is studied. When the solution pH is relatively low, the protein can adsorb to the SAM surface. Such adhesion is attributed to several salt bridges between acidic residues and SAM's protonated groups, and there are water molecules distributed under the adsorbed protein, i.e. interlayer water. Interestingly, the increase of the solution pH reduces the binding affinity of the protein, which engenders the lateral diffusion of the protein and the increase of interlayer water. When the solution pH is further increased, the enhanced lateral diffusion of the protein and the growth of interlayer water disrupt the formation of salt bridges between the protein and the SAM, and the protein progressively dissociates from the SAM. The spontaneous desorption process of the protein and the corresponding mechanisms illustrated in this work may be helpful to develop an antifouling surface and enhance the biosafety of nanomaterials.