Induction of mTOR-dependent Autophagy by WS2 Nanosheets from both Inside and Outside of Human Cells
Applications of two-dimensional transition metal dichalcogenides (2D TMDCs) increase both their environment pollution and risks to human health. Due to large surface areas of 2D nanosheets, they often form multi-layered nano clusters of various thicknesses in aqueous solutions. In this work, we address the safety issue of 2D TMDCs with a focus on the cellular effects of thickness of WS2 nanosheets. At a very low and non-lethal concentration (4 cm2/mL or 25 μg/mL), 4-layered WS2 nanosheets (WS2-4) primarily bound to cell surface with less internalization, while 30-layered WS2 nanosheets (WS2-30) were mostly internalized by human bronchial epithelial cells. Although cellular interactions at this low concentration caused no alterations in cell cycle, apoptosis, necrosis or cytotoxicity, cell autophagy was induced in both cases through mTOR-dependent pathways by perturbing a number of signaling molecules, such as amyloid precursor protein (APP) and cysteine-X-cysteine chemokine receptor 4 (CXCR-4). The finding of activation of cell autophagy from both outside and inside of cells reveals a novel feature of biological perturbations by 2D nanosheets. At the same time, this finding will help make general guidelines for safe applications of 2D nanomaterials.
- This article is part of the themed collection: 2019 Nanoscale HOT Article Collection