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.