(229bj) Substrate Physical Cues Regulated Fibroblasts Sensing Carbon Nanotubes

While the rapidly evolving nanotechnology has shown promise in electronics, energy, healthcare and many other fields, there is an increasing concern about the adverse health consequences of engineered nanomaterials. It has been shown that inhaled carbon nanotubes (CNTs) rapidly enter the lung interstitium to stimulate collagen production and induce progressive interstitial lung fibrosis in weeks in mice. The lung interstitium displays interrelated framework of nanoscale fibrous proteins. The lung has stiffness ranging from £ 5 kPa for native lung tissue to 25 â?? 100 kPa for fibrotic tissues. The majority of current in vitro models lack characteristics of in vivo microenvironment, leading to the cell behavior deviated from in vivo phenotypes and responsiveness. We hypothesize that substrate nanotopography and stiffness cues can affect toxic response of cells to nanomaterials. We thus engineered polydimethylsiloxane (PDMS) nanotopographies of different shapes and dimensions and polyacrylamide (PAAm) gels of various stiffnesses, and investigated how the physical cues influenced fibrogenic response, including cell spreading, proliferation, collagen I production and reactive oxygen species generation of normal human lung fibroblasts to multi-walled carbon nanotubes (MWCNTs). The results show that the substrate physical cues can regulate cell spreading and intracellular tension, and consequently affect toxic response of the fibroblasts to the CNTs. When the cells are less spread, the cellular sensitivity to the CNTs is enhanced. This study highlights the important role of cell-substrate interactions in fibrogenic response of the fibroblasts to nanomaterials, and contributes to development of physiologically relevant in vitro models for nanotoxicology study.