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

Abstract

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.

Keywords:

• Single-layer molybdenum disulfide
• proliferation
• differentiation
• Akt-dependent signaling pathway
• protein corona

Disclosure statement

The authors declare no competing financial interests.

Additional information

Funding

This work was financially supported by the National Natural Science Foundation of China [Grant nos. 21577070 and 21407085], the Tianjin Natural Science Foundation [Grant no. 16JCQNJC08400], the State Key Laboratory of Pollution Control and Resource Reuse Foundation [Grant no. PCRRF16023], the Fundamental Research Funds for the Central Universities [Grant no. 63171224], the Hundred young academic leaders training program [Grant no. 63174011], and the Postdoctoral Science Foundation of China [Grant nos. 2014M550138 and 2015T80215].