Publikationsrepositorium - Helmholtz-Zentrum Dresden-Rossendorf

A comprehensive understanding of molecular events leading to adverse outcomes in lungs after administration of ultrafine particulate matter (PM) is still lacking. These repeating exposures to the respiratory tract can eventually lead to persistent inflammation and further cardiovascular diseases (Li et al 2019, Underwood 2017). To better identify and characterize the initial sub-cellular to molecular events after nanomaterial contact, which triggers all following cascades leading to acute or even chronic inflammation, one urgently needs an appropriate high-resolution experimental approach to untangle these key processes.
In our first study focused on how metal oxide aerosols (TiO2) effect model lung epithelium we thus applied super-resolution STED microscopy together with fluorescence microspectroscopy (FMS), where we showed nanoparticle wrapping of cell membranes followed by their translocation across the cell layer (Figure 1) supporting the proposed causal link between the inhalation of nanoparticles and cardiovascular disease (Urbančič et al 2018). But to get more insight into complex and likely destructive nanoparticle interaction with biological matter our next aim was to identify and characterize individual paramount cellular responses by observing real-time structural changes implementing advanced correlative microscopy (CM) approach.
In one of our latest studies, we thus introduced a new CM pipeline, combining STED multimodal microscopy with helium ion microscopy (HIM), which revealed the morphology and the extent of biological wrapping of quarantined nanomaterial composites on the epithelium surface decisive for the onset of chronic inflammation on single molecule scale (Kokot et al 2020) (Figure 2).