  Upon introduction into a biological system, engineered nanomaterials (ENMs)
rapidly associate with a variety of biomolecules such as proteins and lipids to
form a biocorona. The presence of biocorona influences nano-bio interactions
considerably, and could ultimately result in altered biological responses.
Apolipoprotein A-I (ApoA-I), the major constituent of high-density lipoprotein
(HDL), is one of the most prevalent proteins found in ENM-biocorona
irrespective of ENM nature, size, and shape. Given the importance of ApoA-I in
HDL and cholesterol transport, it is necessary to understand the mechanisms of
ApoA-I adsorption and the associated structural changes for assessing
consequences of ENM exposure. Here, we used a comprehensive array of
microscopic and spectroscopic tools to elucidate the interactions between
ApoA-I and 100 nm Ag nanoparticles (AgNPs) with four different surface
functional groups. We found that the protein adsorption and secondary
structural changes are highly dependent on the surface functionality. Our
electrochemical studies provided new evidence for charge transfer interactions
that influence ApoA-I unfolding. While the unfolding of ApoA-I on AgNPs did not
significantly modify their cellular uptake and short-term cytotoxicity, we
observed that it strongly altered the ability of only some AgNPs to generate
reactive oxygen species in macrophages. Our results shed new light on the
importance of surface functionality and charge transfer interactions in
biocorona formation.
