Unveiling the effects of protein corona formation on the aggregation kinetics of gold nanoparticles in monovalent and divalent electrolytes

Elucidation of the aggregation behaviors of gold nanoparticles (AuNPs) in water systems is crucial to understanding their environmental fate and transport as well as human health effects. We investigated the early-stage aggregation kinetics of AuNPs coated by human serum albumin (HSA) protein corona (PC) in NaCl and CaCl2 through time-resolved dynamic light scattering. We found that the aggregation of PC-AuNPs depended on the concerted effects of electrolyte concentration, valence, and HSA concentration. At low HSA concentration (<= 0.005 g/L), the aggregation kinetics of PC-AuNPs was similar to that of bare AuNPs due to insignificant HSA adsorption. At intermediate HSA concentrations of 0.025-0.050 g/L, the aggregation of PC-AuNPs was retarded in both electrolytes due to steric repulsive forces imparted by the PCs. Additionally, HSA PCs had a weaker retardation effect on PC-AuNPs aggregation in divalent than in monovalent electrolytes. Quartz crystal microbalance measurements revealed that the presence of Ca2+ promoted additional HSA adsorption on PC-AuNPs likely via -COO-Ca2+ bond, and eventually enhanced the aggregation between PC-AuNPs. High-concentration HSA (>0.5 g/L) resulted in no PC-AuNPs aggregation regardless of electrolyte valence and concentrations. Finally, desorption of HSA barely occurred after adsorption on the gold surface, suggesting that the formation of PC-AuNPs is mostly irreversible.