Cellular proliferation and differentiation induced by single-layer molybdenum disulfide and mediation mechanisms of proteins via the Akt-mTOR-p70S6K signaling pathway

Single-layer molybdenum disulfide (SLMoS₂) is a novel kind of 2D nanosheet that has attracted great attention regarding its use in biosensors, drug delivery, tissue engineering, and therapy. However, our results demonstrated that SLMoS₂ accelerated proliferation and promoted myogenic differentiation and epithelial–mesenchymal transition (EMT) in human embryonic lung fibroblasts (HELFs). The abnormal proliferation and differentiation of HELFs contribute to idiopathic pulmonary fibrosis. Specifically, SLMoS₂ significantly stimulated the expression of myofibroblast- and mesenchymal-associated genes and proteins. The Akt-mTOR-p70S6K signaling pathway plays a critical role in the acceleration of proliferation and promotion of myogenic differentiation and EMT in HELFs induced by SLMoS₂. After cell uptake, SLMoS₂ was primarily located in the cytoplasm and the perinuclear region and activated Akt-dependent signaling due to the generation of reactive oxygen species (ROS). Moreover, bovine serum albumin (BSA) binding markedly inhibited the cellular uptake of SLMoS₂ and the production of intracellular ROS due to an increased thickness and reduced adhesion of HELFs. BSA binding also mitigated the SLMoS₂-activated phosphorylation of Akt-dependent signaling pathways. This study is the first to illustrate the induction of cellular proliferation and differentiation by SLMoS₂ and the related mediation by proteins through Akt-mTOR-p70S6K signaling pathway.