Mechanistic Insights of TiO₂ Nanoparticles with Different Surface Charges on Aβ₄₂ Peptide Early Aggregation: An In Vitro and In Silico Study

Abstract

Humans may intendedly or unintendedly be exposed to nanomaterials through food, water, and air. Upon exposure, nanomaterials can pierce the bloodstream and translocate to secondary organs, including the brain, which warrants increased concern for the potential health impacts of nanomaterials. Due to their large surface area and interaction energy, nanomaterials can adsorb surrounding proteins. The misfolding and self-aggregation of amyloid-β (Aβ) have been considered significant factors in the pathogenesis of Alzheimer's disease. We thus hypothesize that braintargeted nanomaterials may modulate Aβ aggregation and cause related neurotoxicity. Here, we showed that TiO 2 nanoparticles (NPs) and their aminated analogue (TiO 2 -NH 2 NPs) adsorb the Aβ 42 peptide and accelerate its early oligomerization. Molecular dynamics simulation indicated that the adsorption onto TiO 2 NPs and TiO 2 -NH 2 NPs surfaces can stabilize the β-sheet-rich conformations formed by the Aβ 42 peptide. The binding sites between TiO 2 -NH 2 NPs and the Aβ 42 oligomer surface were mainly concentrated in the hydrophobic core region, and the β-sheet conformation spontaneously formed by Aβ 42 oligomers can be better stabilized through a hydrogen bond, electrostatic attraction, and hydrophobic interaction. This study will further help in the understanding of nanomaterial-related neurotoxicities and the regulation of their applications.

A Feasibility Study on Enhanced Oil Recovery of Modified Janus Nano Calcium Carbonate-Assisted Alkyl Polyglycoside to Form Nanofluids in Emulsification Flooding

“…This was due to the fact that one end of JNC-12 particle surface contained OH groups, and the other end contained long chain alkyl groups. Because of these lipophilic groups, the moisture in the air cannot adsorb onto the surface of Nano CaCO 3 , so JNC-12 particles are difficult to agglomerate. − The micromorphologies of nanoparticles (500 ppm) in APG solution (1000 ppm) is shown in Figure . It can be found that Nano CaCO 3 particles aggregated together in APG solution, but JNC-12 could uniformly disperse in APG solution.…”

From Mechanisms to Implications: Understanding the Molecular Neurotoxicity of Titanium Dioxide Nanoparticles

“…Direct interaction between TiO 2 NPs and β-amyloid significantly increased amyloid aggregation and fibrillation, as well as induced conformational changes in α-synuclein molecule when incubated at 37 °C [127]. Correspondingly, absorption of Aβ42 peptide on TiO 2 NPs and its aminated derivative TiO 2 -NH 2 NPs promoted early protein oligomerization [128].…”