Abstract

The surface of nanoparticles (NPs) get coated by a wide range of biomolecules, upon exposure to biological fluids. It is now being increasingly accepted that NPs with particular physiochemical properties have a capacity to induce conformational changes to proteins and therefore influence their biological fates, we hypothesized that the gold NP’s metal surface may also be involved in the observed Fg unfolding and inflammatory response. To mechanistically test this hypothesis, we probed the interaction of Fg with gold surfaces using molecular dynamic simulation (MD) and revealed that the gold surface has a capacity to induce Fg conformational changes in favor of inflammation response. As the integrity of coatings at the surface of ultra-small gold NPs are not thorough, we also hypothesized that the ultra-small gold NPs have a capacity to induce unfolding of Fg regardless of the composition and surface charge of their coatings. Using different surface coatings at the surface of ultra-small gold NPs, we validated this hypothesis. Our findings suggest that gold NPs may cause unforeseen inflammatory effects, as their surface coatings may be degraded by physiological activity.

Highlights

  • The surface of nanoparticles (NPs) get coated by a wide range of biomolecules, upon exposure to biological fluids

  • The protein-NP interactions leading to corona formation are not limited to electrostatic attractions; under certain conditions, proteins may penetrate the organic molecules on the NP surface and interact with the NP core

  • The main hypothesis of this study is that the observed unfolding of the Fg protein by 5 nm negatively charged PAA-coated gold NPs could be due to penetration of Fg in the PAA brushes and its accessibility to the surface of gold NPs

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Summary

Introduction

The surface of nanoparticles (NPs) get coated by a wide range of biomolecules, upon exposure to biological fluids. It is being increasingly accepted that NPs with particular physiochemical properties have a capacity to induce conformational changes to proteins and influence their biological fates, we hypothesized that the gold NP’s metal surface may be involved in the observed Fg unfolding and inflammatory response. The main hypothesis of this study is that the observed unfolding of the Fg protein by 5 nm negatively charged PAA-coated gold NPs could be due to penetration of Fg in the PAA brushes and its accessibility to the surface of gold NPs. In other words, we hypothesized that both the bare surface of gold NP’s and specific organic coatings are responsible for the observed inflammatory response

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