Direct observation of silver nanoparticle-ubiquitin corona formation

F. Ding
Clemson University, US

Keywords: nanoparticle-protein corona, multiscale molecular dynamics, stretched-exponential binding kinetics, conformational change, nanotoxicity


The advancement of nanomedicine and the increasing applications of nanoparticles in consumer products have led to administered biological exposure and unintentional environmental accumulation of nanoparticles, causing concerns over the biocompatibility and sustainability of nanotechnology. Upon entering physiological environments, nanoparticles readily assume the form of a nanoparticle-protein corona that dictates their biological identity. Consequently, understanding the structure and dynamics of nanoparticle-protein corona is essential for predicting the fate, transport, and toxicity of nanomaterials in living systems and for enabling the vast applications of nanomedicine. We combined multiscale molecular dynamics simulations and complementary experiments to characterize the silver nanoparticle-ubiquitin corona formation. Specifically, ubiquitins competed with citrates for the nanoparticle surface and bound to the particle in a specific manner. The specific binding between a silver nanoparticle and ubiquitin is governed by electrostatic interactions as observed in previous experiments. Under a high protein/nanoparticle stoichiometry, ubiquitins formed a multi-layer corona on the particle surface. The binding exhibited an unusual stretched-exponential behavior, suggesting a rich kinetics originated from protein-protein, protein-citrate, and protein-nanoparticle interactions. Furthermore, the binding destabilized the α-helices while increasing the β-sheets of the proteins. Our results revealed the structural and dynamic complexities of nanoparticle-protein corona and shed light on the origin of nanotoxicity.