Unravelling the Biophysical Mechanism of Lung Surfactant Monolayer Exposed to Gold Nanoparticles Using Molecular Dynamics Simulations

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Air-borne nanoparticles (NPs) can act as pollutants and have harmful effects, yet at the same time, the recent improvements in nanotechnology have enabled the design of NPs with specific properties, and their use in various biomedical applications. For example, gold NPs (AuNPs) found in mining dust or exhaust fumes can cause serious lung diseases but are also used as nanocarriers to improve the delivery of drugs into cells. For air-borne NPs, the main route of entry to the body is via the lungs. After inhalation, the NPs come into contact with the inner surface of the lungs’ alveolus, a component called the lung surfactant (LS). The main site of interaction of inhaled NPs is the LS monolayer, which is composed of lipids and proteins and forms the air-liquid interface of the lungs. Normal physiological lung function depends on the LS monolayer’s capacity to act as a surface tension reducer. Despite exhaustive studies, the molecular-level mechanisms that underpin the adsorption, interaction and translocation/diffusion of AuNPs, either in their bare (pollutants) or phospholipid/ligand-coated (nanocarriers) states, into the LS monolayer are still poorly understood. In this project, a series of coarse-grained molecular dynamics simulations are performed to elucidate the interaction of bare and phospholipid-wrapped AuNPs with LS monolayers, resulting in a number of key findings. First, bare AuNPs structurally deform the LS monolayer in a concentration-dependent manner, changing the biophysical properties of the monolayer, and creating pores in the monolayer. All of these changes are likely to interfere with normal lung functions such as maintaining physiological surface tensions at the interface. Second, the simulations reveal that the surfactant protein B (SP-B₁₋₂₅) found in LS monolayers, is important for monolayer stability and significantly increases AuNP aggregation in the monolayer. Third, phospholipid-wrapped AuNPs further increase the aggregation of SP-B₁₋₂₅, inducing buckle in the monolayer, and participating in the cholesterol sequestration. The studies also explore how the adsorption of phospholipid-wrapped AuNPs and monolayer perturbation are affected by the monolayer breathing conditions, monolayer lipid composition, and nature of the phospholipids used for wrapping. In summary, the combined findings from these simulation studies have provided molecular-level insight into the structure and dynamics of the LS monolayer and how bare or phospholipid-wrapped AuNPs interact with and diffuse into the LS monolayer. The molecular insights of these studies will facilitate the future design of nanocarriers for drug delivery and the assessment of AuNP as a pollutant and thus help to identify potential health risk in people exposed to bare AuNPs.
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