Direct observation of silver nanoparticle-ubiquitin corona formation

TL;DR

This study combines simulations and experiments to reveal how ubiquitin proteins form a complex, multi-layered corona on silver nanoparticles, affecting their structure and potential toxicity in biological environments.

Contribution

It provides detailed insights into the molecular mechanisms and kinetics of ubiquitin corona formation on silver nanoparticles, a novel understanding in nanomedicine.

Findings

Ubiquitins compete with citrates for nanoparticle binding.

A multi-layer corona forms at high protein/nanoparticle ratios.

Protein binding alters secondary structures, increasing β-sheets.

Abstract

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. Under a high protein/nanoparticle stoichiometry, ubiquitions 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 {\alpha}-helices while increasing the {\beta}-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.