title: Carbon nanotube-induced loss of multicellular chirality on micropatterned substrate is mediated by oxidative stress.
abstract: Carbon nanotubes (CNTs) are receiving much attention in medicine, electronics, consumer products, and next-generation nanocomposites because of their unique nanoscale properties. However, little is known about the toxicity and oxidative stress related anomalies of CNTs on complex multicellular behavior. This includes cell chirality, a newly discovered cellular property important for embryonic morphogenesis and demonstrated by directional migration and biased alignment on micropatterned surfaces. In this study, we report the influence of single-walled carbon nanotubes (SWCNTs) on multicellular chirality. The incubation of human umbilical vein endothelial cells (hUVECs) and mouse myoblasts (C2C12) with CNTs at different doses and time points stimulates reactive oxygen species (ROS) production and intra- and extracellular oxidative stress (OS). The OS-mediated noxious microenvironment influences vital subcellular organelles (e.g., mitochondria and centrosomes), cytoskeletal elements (microtubules), and vinculin rich focal adhesions. The disorientated nuclear-centrosome (NC) axis and centriole disintegration lead to a decreased migration rate and loss of directional alignment on micropatterned surfaces. These findings suggest that CNT-mediated OS leads to loss of multicellular chirality. Furthermore, the in vitro microscale system presented here to measure cell chirality can be extended as a prototype for testing toxicity of other nanomaterials.
authors.affiliation: Department of Biomedical Engineering, Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute , Troy, New York 12180, United States.
authors.forename: Ajay V
authors.initials: AV
authors.lastname: Singh
authors.forename: Krunal K
authors.initials: KK
authors.lastname: Mehta
authors.forename: Kathryn
authors.initials: K
authors.lastname: Worley
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Dordick
authors.forename: Ravi S
authors.initials: RS
authors.lastname: Kane
authors.forename: Leo Q
authors.initials: LQ
authors.lastname: Wan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D018385:Centrosome / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D022001:Focal Adhesions / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D051379:Mice; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D037742:Nanotubes, Carbon / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D018675:Toxicity Tests
chemical_list: D000975:Antioxidants; D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species