MSN, MWCNT and ZnO nanoparticle-induced CHO-K1 cell polarisation is linked to cytoskeleton ablation

Abstract Background The cellular response to nanoparticles (NPs) for the mechanical clue and biochemical changes are unexplored. Here, we provide the comprehensive analysis of the Chinese Hamster Ovary (CHO-K1) cell line to study cell behaviour following the exposure of mesoporous silica nanoparticl...

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Main Authors: Karmveer Yadav, Syed Azmal Ali, Ashok Kumar Mohanty, Eshwarmoorthy Muthusamy, Kesavan Subaharan, Gautam Kaul
Format: Article
Language:English
Published: BMC 2021-02-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:https://doi.org/10.1186/s12951-021-00779-7
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author Karmveer Yadav
Syed Azmal Ali
Ashok Kumar Mohanty
Eshwarmoorthy Muthusamy
Kesavan Subaharan
Gautam Kaul
author_facet Karmveer Yadav
Syed Azmal Ali
Ashok Kumar Mohanty
Eshwarmoorthy Muthusamy
Kesavan Subaharan
Gautam Kaul
author_sort Karmveer Yadav
collection DOAJ
description Abstract Background The cellular response to nanoparticles (NPs) for the mechanical clue and biochemical changes are unexplored. Here, we provide the comprehensive analysis of the Chinese Hamster Ovary (CHO-K1) cell line to study cell behaviour following the exposure of mesoporous silica nanoparticle (MSN), multiwall carbon nanotubes (MWCNTs), and zinc oxide (ZnO) NPs. Results Through the high-throughput proteomic study, we observed that the effect of NPs is alone not restricted to cell viability but also on cell polarisation. In the case of MSN, no drastic changes were observed in cellular morphology, but it upregulated chaperons that might prevent protein aggregation. However, MWCNT showed elongated cell appearance with numerous cytoplasmic vacuoles, and induce lamellipodia formation through actin polymerisation. The cytoskeleton remodelling was accompanied by the increased expression of Dlc-1, cofilin and Rac1 proteins. While ZnO NPs resulted in the rounded cell morphology along with nuclear abnormalities. The proteome analysis revealed that UBXN11 control cell roundness and DOCK3 leads to actin stress fibre formation and finally, loss of cell adhesion. It enhances the expression of catastrophic DNA damage and apoptotic proteins, which was unrecoverable even after 72 h, as confirmed by the colony formation assay. All three NPs trigger over-expression of the endocytic pathway, ubiquitination, and proteasomal complex proteins. The data indicate that ZnO and MSN entered into the cells through clathrin-mediated pathways; whereas, MWCNT invades through ER-mediated phagocytosis. Conclusions Based on the incubation and concentration of NPs, our work provides evidence for the activation of Rac-Rho signalling pathway to alter cytoskeleton dynamics. Our results assist as a sensitive early molecular readout for nanosafety assessment.
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spelling doaj.art-c1a874f1cfb149618e5c7d53757f5a842022-12-22T03:08:46ZengBMCJournal of Nanobiotechnology1477-31552021-02-0119112410.1186/s12951-021-00779-7MSN, MWCNT and ZnO nanoparticle-induced CHO-K1 cell polarisation is linked to cytoskeleton ablationKarmveer Yadav0Syed Azmal Ali1Ashok Kumar Mohanty2Eshwarmoorthy Muthusamy3Kesavan Subaharan4Gautam Kaul5N.T. Lab-1, Division of Animal Biochemistry, ICAR-National Dairy Research InstituteCell Biology and Proteomics Lab, Animal Biotechnology Centre, National Dairy Research InstituteCell Biology and Proteomics Lab, Animal Biotechnology Centre, National Dairy Research InstituteChemistry and Physics of Materials Unit, Jawaharlal Nehru Centre for Advanced Scientific ResearchDivision of Germplasm, Conservation and Utilisation, National Bureau of Agricultural Insect ResourcesN.T. Lab-1, Division of Animal Biochemistry, ICAR-National Dairy Research InstituteAbstract Background The cellular response to nanoparticles (NPs) for the mechanical clue and biochemical changes are unexplored. Here, we provide the comprehensive analysis of the Chinese Hamster Ovary (CHO-K1) cell line to study cell behaviour following the exposure of mesoporous silica nanoparticle (MSN), multiwall carbon nanotubes (MWCNTs), and zinc oxide (ZnO) NPs. Results Through the high-throughput proteomic study, we observed that the effect of NPs is alone not restricted to cell viability but also on cell polarisation. In the case of MSN, no drastic changes were observed in cellular morphology, but it upregulated chaperons that might prevent protein aggregation. However, MWCNT showed elongated cell appearance with numerous cytoplasmic vacuoles, and induce lamellipodia formation through actin polymerisation. The cytoskeleton remodelling was accompanied by the increased expression of Dlc-1, cofilin and Rac1 proteins. While ZnO NPs resulted in the rounded cell morphology along with nuclear abnormalities. The proteome analysis revealed that UBXN11 control cell roundness and DOCK3 leads to actin stress fibre formation and finally, loss of cell adhesion. It enhances the expression of catastrophic DNA damage and apoptotic proteins, which was unrecoverable even after 72 h, as confirmed by the colony formation assay. All three NPs trigger over-expression of the endocytic pathway, ubiquitination, and proteasomal complex proteins. The data indicate that ZnO and MSN entered into the cells through clathrin-mediated pathways; whereas, MWCNT invades through ER-mediated phagocytosis. Conclusions Based on the incubation and concentration of NPs, our work provides evidence for the activation of Rac-Rho signalling pathway to alter cytoskeleton dynamics. Our results assist as a sensitive early molecular readout for nanosafety assessment.https://doi.org/10.1186/s12951-021-00779-7ApoptosisCell morphologyCytoskeleton dynamicsER-mediated phagocytosis and nanoparticles
spellingShingle Karmveer Yadav
Syed Azmal Ali
Ashok Kumar Mohanty
Eshwarmoorthy Muthusamy
Kesavan Subaharan
Gautam Kaul
MSN, MWCNT and ZnO nanoparticle-induced CHO-K1 cell polarisation is linked to cytoskeleton ablation
Journal of Nanobiotechnology
Apoptosis
Cell morphology
Cytoskeleton dynamics
ER-mediated phagocytosis and nanoparticles
title MSN, MWCNT and ZnO nanoparticle-induced CHO-K1 cell polarisation is linked to cytoskeleton ablation
title_full MSN, MWCNT and ZnO nanoparticle-induced CHO-K1 cell polarisation is linked to cytoskeleton ablation
title_fullStr MSN, MWCNT and ZnO nanoparticle-induced CHO-K1 cell polarisation is linked to cytoskeleton ablation
title_full_unstemmed MSN, MWCNT and ZnO nanoparticle-induced CHO-K1 cell polarisation is linked to cytoskeleton ablation
title_short MSN, MWCNT and ZnO nanoparticle-induced CHO-K1 cell polarisation is linked to cytoskeleton ablation
title_sort msn mwcnt and zno nanoparticle induced cho k1 cell polarisation is linked to cytoskeleton ablation
topic Apoptosis
Cell morphology
Cytoskeleton dynamics
ER-mediated phagocytosis and nanoparticles
url https://doi.org/10.1186/s12951-021-00779-7
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