TiO₂ Nanoparticle-Induced Oxidation of the Plasma Membrane: Importance of the Protein Corona

Abstract

Titanium dioxide (TiO) nanoparticles, used as pigments and photocatalysts, are widely present in modern society. Inhalation or ingestion of these nanoparticles can lead to cellular-level interactions. We examined the very first step in this cellular interaction, the effect of TiO nanoparticles on the lipids of the plasma membrane. Within 12 h of TiO nanoparticle exposure, the lipids of the plasma membrane were oxidized, determined with a malondialdehyde assay. Lipid peroxidation was inhibited by surface passivation of the TiO nanoparticles, incubation with an antioxidant (Trolox), and the presence of serum proteins in solution. Subsequent experiments determined that serum proteins adsorbed on the surface of the TiO nanoparticles, forming a protein corona, inhibit lipid peroxidation. Super-resolution fluorescence microscopy showed that these serum proteins were clustered on the nanoparticle surface. These protein clusters slow lipid peroxidation, but by 24 h, the level of lipid peroxidation is similar, independent of the protein corona or free serum proteins. Additionally, over 24 h, this corona of proteins was displaced from the nanoparticle surface by free proteins in solution. Overall, these experiments provide the first mechanistic investigation of plasma membrane oxidation by TiO nanoparticles, in the absence of UV light and as a function of the protein corona, approximating a physiological environment.

Super-resolution microscopy as a powerful tool to study complex synthetic materials

“…The study revealed that the proteins tend to form patches rather than homogenously cover the surface of the nanoparticles. SRM also helped to understand the protein corona turnover, which was complete after 24 hours, even for the hard corona, the layer formed by low abundance, higher affinity proteins.Protein corona on nanoparticles might have a positive effect as it can prevent plasma membrane lipid oxidation 141 . Lipid peroxidation resulted to be equally inhibited by an alumina-silica shell, by the presence of an antioxidant (Trolox) , as well as by the protein corona.…”

TiO2 nanoparticles generate superoxide and alter gene expression in human lung cells

“…These results support our previous ndings that TiO 2 NPs cause cellular oxidation without UV exposure. 15,24,33 Analysis of the RNA-Seq data for Generation 1, Generation 10, and re-challenged cells identied oxidative stress-related genes with greater than two-fold change upon TiO 2 NP exposure (Table 3; p < 0.05, compared to an untreated control).…”

Nanoparticle–Cell Interactions: Relevance for Public Health

“…61 Similarly, the direct incubation of “bare” TiO 2 NPs, lacking a protein corona, with cells led to oxidation of plasma membrane lipids (156 ± 5% increase, MDA assay). 50 …”

“…Copyright 2016 American Chemical Society. Bottom right reprinted with permission from ref (50). Copyright 2017 American Chemical Society.…”