4.5 Article

Mechanical cues protect against silica nanoparticle exposure in SH-SY5Y neuroblastoma

Journal

TOXICOLOGY IN VITRO
Volume 70, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2020.105031

Keywords

Toxicity; Neuroblastoma; Cytoskeleton; Silica; Extracellular matrix; ROS

Categories

Funding

  1. Iowa Recruitment Fellowship
  2. National Institute for Environmental Health Sciences through the University of Iowa Environmental Health Sciences Research Center [NIEHS/NIH P30 ES005605]
  3. NIH grant [1S10 RR025439-01]

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Exposure to amorphous silica particles can destabilize mitochondrial membrane potential, stimulate ROS production, and promote cytotoxicity in SH-SY5Y human neuroblastoma cells. The mechanical environment significantly impacts silica nanoparticle toxicity, with cells on softer matrix showing better viability and lower ROS production compared to those plated on stiffer matrix. This study highlights the importance of mechanobiochemical mechanisms at the cell-matrix interface in regulating nanotoxicity.
The increasing appearance of engineered nanomaterials in broad biomedical and industrial sectors poses an escalating health concern from unintended exposure with unknown consequences. Routine in vitro assessments of nanomaterial toxicity are a vital component to addressing these mounting health concerns; however, despite the known role of cell-cell and cell-matrix contacts in governing cell survival, these physical interactions are generally ignored. Herein, we demonstrate that exposure to amorphous silica particles destabilizes mitochondrial membrane potential, stimulates reactive oxygen species (ROS) production and promotes cytotoxicity in SH-SY5Y human neuroblastoma through mechanisms that are potently matrix dependent, with SH-SY5Y cells plated on the softest matrix displaying a near complete recovery in viability compared to dose-matched cells plated on tissue-culture plastic. Cells on the softest matrix (3 kPa) further displayed a 50% reduction in ROS production and preserved mitochondrial membrane potential. The actin cytoskeleton is mechanosensitive and closely related to ROS production. SH-SY5Y cells exposed to a 100 mu g/mL dose of 50 nm silica particles displayed distinct cytoskeletal aberrations and a 70% increase in cell stiffness. Overall, this study establishes that the mechanical environment can significantly impact silica nanoparticle toxicity in SH-SY5Y cells. The mechanobiochemical mechanisms behind this regulation, which are initiated at the cell-matrix interface to adjust cytoskeletal structure and intracellular tension, demand specific attention for a comprehensive understanding of nanotoxicity.

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