Remote Induction of Cell Autophagy by 2D MoS₂ Nanosheets via Perturbing Cell Surface Receptors and mTOR Pathway from Outside of Cells

The ability of nanoparticles to induce adverse consequences in human cells relies on their physical shapes. In this aspect, how two-dimensional nanoparticles differ from three-dimensional nanoparticles is not well-known. To elucidate this difference, combined experimental and theoretical approaches are employed to compare MoS2 nanosheets with 5-layer and 40-layer thicknesses for their cellular effects and the associated molecular events. At a concentration as defined by the nanosheet surface areas (10 cm2/mL), 40-layer nanosheets are internalized by cells, whereas 5-layer nanosheets mostly bind to the cell surface without internalization. Although they alter different autophagy-related genes, a common mechanism is that they both perturb cell surface protein amyloid precursor proteins and activate the mTOR signaling pathway. Our findings prove that the perturbation of cellular function without nanoparticle internalization has significant nanomedicinal and nanotoxicological significances.