Direct observation of nanoparticle-ubiquitin corona formation

Upon entering physiological environments, nanoparticles readily assume the form of a nanoparticle-protein corona that dictates their biological identity. 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 multilayer corona on the particle surface. The binding exhibited a stretched-exponential behavior, suggesting a rich protein-nanoparticle binding kinetics. Furthermore, the binding destabilized the a-helices while increasing the β-sheets of the proteins. Our results revealed the structural and dynamic complexities of nanoparticle-protein corona formation and shed light on the origin of nanotoxicity.