Amorphous aggregation of tau in the presence of titanium dioxide nanoparticles: biophysical, computational, and cellular studies

Abstract

Background

Nanoparticles (NPs) when injected into the body can reach target tissues like nervous system and interact with tau proteins and neurons. This can trigger conformational changes of tau and may affect NP toxicity.

Methods

In this study, we used several biophysical techniques (extrinsic and intrinsic fluorescence spectroscopy, circular dichroism (CD) spectroscopy, ultraviolet (UV)-visible spectroscopy), transmission electron microscopy (TEM) investigations, molecular docking and molecular dynamics studies, and cellular assays [3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) and flow cytometry) to reveal how structural changes of tau protein can change the cytotoxicity of titanium dioxide (TiO₂) NPs against neuron-like cells (SH-SY5Y) cells.

Results

It was shown that TiO₂ NPs result in hydrophilic interactions, secondary and tertiary structural changes, and the formation of amorphous tau aggregates. Conformational changes of tau increased the induced cytotoxicity by TiO₂ NPs. These data revealed that the denatured adsorbed protein on the NP surface may enhance NP cytotoxicity.

Conclusion

Therefore, this study provides useful insights on the NP–protein interactions and discusses how the protein corona can increase cytotoxicity to determine the efficacy of targeted delivery of nanosystems.

Keywords:

• titanium oxide nanoparticle
• tau
• amorphous aggregation
• cytotoxicity
• neuron- like cells

Acknowledgments

The financial support of Tehran Medical Sciences, Islamic Azad University, Tehran, Iran is greatly acknowledged.

Disclosure

The authors report no conflicts of interest in this work.