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

Kendra J Bell; Thiranjeewa I Lansakara; Rachel Crawford; T. Blake Monroe; Alexei V Tivanski; Aliasger K Salem; Lewis L Stevens

doi:10.1016/j.tiv.2020.105031

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

Journal article

Peer reviewed

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

Kendra J Bell, Thiranjeewa I Lansakara, Rachel Crawford, T. Blake Monroe, Alexei V Tivanski, Aliasger K Salem and Lewis L Stevens

Toxicology in vitro, Vol.70, pp.105031-105031

02/2021

DOI: 10.1016/j.tiv.2020.105031

PMCID: PMC7877221

PMID: 33075489

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https://www.ncbi.nlm.nih.gov/pmc/articles/7877221View

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Abstract

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 μg/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. •ROS-mediated silica toxicity in neuroblastoma is mechanosensitive.•Exposure to silica nanoparticles prompts cytoskeletal reorganization and cell stiffening.•Cells plated on soft matrices blunt ROS from silica to improve viability.•Mitochondrial membrane potential is better preserved in soft cells exposed to silica.

Cytoskeleton

Extracellular matrix

Neuroblastoma

ROS

Silica

Toxicity

Details

Title: Subtitle: Mechanical cues protect against silica nanoparticle exposure in SH-SY5Y neuroblastoma
Creators: Kendra J Bell - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, United States of America
Thiranjeewa I Lansakara - Department of Chemistry, The University of Iowa, Iowa City, IA 52245, United States of America
Rachel Crawford - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, United States of America
T. Blake Monroe - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, United States of America
Alexei V Tivanski - Department of Chemistry, The University of Iowa, Iowa City, IA 52245, United States of America
Aliasger K Salem - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, United States of America
Lewis L Stevens - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, United States of America
Resource Type: Journal article
Publication Details: Toxicology in vitro, Vol.70, pp.105031-105031
DOI: 10.1016/j.tiv.2020.105031
PMID: 33075489
PMCID: PMC7877221
NLM abbreviation: Toxicol In Vitro
ISSN: 0887-2333
eISSN: 1879-3177
Publisher: Elsevier Ltd
Grant note: DOI: 10.13039/100000066, name: National Institute for Environmental Health Sciences, award: NIEHS/NIH P30 ES005605; name: University of Iowa Environmental Health Sciences Research Center; name: NIH, award: 1S10 RR025439-01
Language: English
Date published: 02/2021
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Chemistry; Dental Research; Chemical and Biochemical Engineering
Record Identifier: 9984216673102771

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