Study of the Disposition of Airborne Particulate Matter at the Respiratory Epithelial Barrier

Exposure to environmental airborne particulate matter has been associated with many lung diseases including fibrosis and lung cancer. The toxicity effects of these particles on the human respiratory system depend on their composition, size and shape and although many studies have been reported on this matter, there is little clarity on the physicochemical factors controlling the particle interactions with the respiratory epithelial barrier and their possible translocation to other body compartments. Here we aim to study the interaction of a series of different size airborne particles with components of the extracellular biological fluids encountered in the respiratory system (i.e. mucus, surfactants, proteins etc.) to gain insights into the adsorption processes occurring at the bio-nanointerface. In fact, the real nano-objects interacting with the respiratory epithelial cell barrier will be not the particles as observed in air particle sampling experiments but will instead be complexes of particles with adsorbed biological fluid components. Inhaled environmental particulates have been shown to cause pro-inflammatory events with increased chemokine production from lung epithelial cells, so it is crucial to understand if this cellular response is positively or negatively affected by the biomolecule (i.e. proteins, lipids, etc.) components of the particle-biomolecule complexes. The study proposed here will include the physicochemical characterization of airborne particulates collected in the UK and the determination of the type of biological molecules that associate with the particles after exposure to the lung lining fluids. With knowledge of the biological material adsorbed on the particles a series of in vitro cell culture experiments will characterise the biological response of lung epithelial cells to particulate matter.