Titanium dioxide nanoparticles alter cellular morphology via disturbing the microtubule dynamics

Abstract

Titanium dioxide (TiO₂) nanoparticles (NPs) have been widely used in our daily lives, for example, in the areas of sunscreens, cosmetics, toothpastes, food products, and nanomedical reagents. Recently, increasing concern has been raised about their neurotoxicity, but the mechanisms underlying such toxic effects are still unknown. In this work, we employed a human neuroblastoma cell line (SH-SY5Y) to study the effects of TiO₂ NPs on neurological systems. Our results showed that TiO₂ NPs did not affect cell viability but induced noticeable morphological changes until 100 μg ml⁻¹. Immunofluorescence detection showed disorder, disruption, retraction, and decreased intensity of the microtubules after TiO₂ NPs treatment. Both α and β tubule expressions did not change in the TiO₂ NP-treated group, but the percentage of soluble tubules was increased. A microtubule dynamic study in living cells indicated that TiO₂ NPs caused a lower growth rate and a higher shortening rate of microtubules as well as shortened lifetimes of de novo microtubules. TiO₂ NPs did not cause changes in the expression and phosphorylation state of tau proteins, but a tau–TiO₂ NP interaction was observed. TiO₂ NPs could interact with tubule heterodimers, microtubules and tau proteins, which led to the instability of microtubules, thus contributing to the neurotoxicity of TiO₂ NPs.