Adsorption and Unfolding of a Single Protein Triggers Nanoparticle Aggregation

TLDR

The protein corona that forms around nanoparticles shortly after exposure to physiological fluids influences a wide range of pathophysiologies, yet a mechanistic understanding of protein–nanoparticle interactions is often lacking because current ensemble methods are inadequate. The study aims to develop strategies to control nanoparticle‑induced pathophysiology in vivo by leveraging new insights and methods. Using single‑molecule and single‑particle spectroscopy alongside ensemble characterization, the authors mapped concentration‑dependent interaction pathways between gold nanorods and bovine serum albumin. Local protein concentration changes affect cancer cell uptake, nanoparticle stability, and protein secondary structure.

Abstract

The response of living systems to nanoparticles is thought to depend on the protein corona, which forms shortly after exposure to physiological fluids and which is linked to a wide array of pathophysiologies. A mechanistic understanding of the dynamic interaction between proteins and nanoparticles and thus the biological fate of nanoparticles and associated proteins is, however, often missing mainly due to the inadequacies in current ensemble experimental approaches. Through the application of a variety of single molecule and single particle spectroscopic techniques in combination with ensemble level characterization tools, we identified different interaction pathways between gold nanorods and bovine serum albumin depending on the protein concentration. Overall, we found that local changes in protein concentration influence everything from cancer cell uptake to nanoparticle stability and even protein secondary structure. We envision that our findings and methods will lead to strategies to control the associated pathophysiology of nanoparticle exposure in vivo.