Cell–Substrate Interactions Lead to Internalization and Localization of Layered MoS2 Nanosheets

Using an ultrathin film substrate, the first internalization of MoS2 nanosheets through mechanotransduction is demonstrated. The usual method of dispersing nanomaterials in the media limits interactions to random, serendipitous surface contact, and the nanoparticles must be dispersible in media. A substrate approach means that cells directly engage with the nanomaterial, sensing and adhering through sustained interaction and actively internalizing the nanomaterial. This activates previously unobserved cell–substrate mechanotransduction mechanisms and receptor-mediated uptake pathways. Moreover, a wide variety of nonsoluble nanomaterials can be used, improving control over the amount of material exposed to a cell through tunable deposition density. Volumetric Raman mapping demonstrates localization of material to the endoplasmic reticulum, a historically hard-to-target region. The nanosheets do not cause cytotoxicity, are transferred to daughter cells, and have applicability across multiple cell lines. The innate fluorescence or Raman signal of the nanosheet can be utilized for live cell imaging, and targeted accumulation within specific cellular organelles offers potential for photothermal treatments or drug delivery vectors. This substrate-mediated approach provides a step change to studying nanomaterial–cellular interactions, taking advantage of the broad palette of available two-dimensional (2D) materials and making use of mechanosensing to stimulate tunable responses, with potential for therapies and diagnostics.