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

Abstract

Aida Fardanesh,1,* Sedigheh Zibaie,1,* Behdad Shariati,1 Farnoosh Attar,2 Fatemeh Rouhollah,1 Keivan Akhtari,3 Koroosh Shahpasand,4 Ali Akbar Saboury,5 Mojtaba Falahati6 1Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 2Department of Biology, Faculty of Food Industry and Agriculture, Standard Research Institute (SRI), Karaj, Iran; 3Department of Physics, University of Kurdistan, Sanandaj, Iran; 4Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; 5Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran; 6Department of Nanotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran *These authors contributed equally to this work 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

Keywords

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