Time Evolution of Ultrasmall Gold Nanoparticle-Protein Interactions

Area of Science:

• Nanotechnology
• Biochemistry
• Materials Science

Background:

• Protein corona formation on large gold nanoparticles (GNPs) is well-studied.
• The protein corona concept is not applicable to ultrasmall GNPs (<3 nm), leaving their protein interactions poorly understood.

Purpose of the Study:

• To systematically investigate ultrasmall GNP (usGNP)-protein interactions, focusing on time-dependent complex formation.
• To understand the effects of usGNPs on protein structure, function, and complex stability.

Main Methods:

• Utilized anionic usGNPs and six model proteins (chymotrypsin, trypsin, thrombin, serum albumin, cytochrome c, factor XII).
• Employed various biochemical and biophysical techniques to assess binding affinities, protein structural/functional changes, reversibility, and complex stability.

Main Results:

• Prolonged (24 h) usGNP exposure permanently altered protein function (enzyme activity, peroxidase-like activity, ligand binding) without significant global conformational changes.
• Both short-term (10 min) and long-term (24 h) interactions resulted in transient complexes, lacking the time-dependent "hardening" seen with larger GNPs.

Conclusions:

• UsGNP interactions with proteins are time-dependent, affecting local conformation or dynamics and leading to functional alterations.
• The lack of complex hardening suggests distinct usGNP-protein interaction mechanisms compared to larger GNPs.
• Findings enhance the fundamental understanding of nano-bio interactions for ultrasmall nanoparticles, aiding their clinical translation.