In adult respiratory distress syndrome, the primary function of pulmonary surfactant to strongly reduce the surface tension of the air-alveolar interface is impaired, resulting in diminished lung compliance, a decreased lung volume, and severe hypoxemia. Dysfunction coincides with an increased level of cholesterol in surfactant which on its own or together with other factors causes surfactant failure. In the current study, we investigated by atomic force microscopy and Kelvin-probe force microscopy how the increased level of cholesterol disrupts the assembly of an efficient film. Functional surfactant films underwent a monolayer-bilayer conversion upon contraction and resulted in a film with lipid bilayer stacks, scattered over a lipid monolayer. Large stacks were at positive electrical potential, small stacks at negative potential with respect to the surrounding monolayer areas. Dysfunctional films formed only few stacks. The surface potential of the occasional stacks was also not different from the surrounding monolayer. Based on film topology and potential distribution, we propose a mechanism for formation of stacked bilayer patches whereby the helical surfactant-associated protein SP-C becomes inserted into the bilayers with defined polarity. We discuss the functional role of the stacks as mechanically reinforcing elements and how an elevated level of cholesterol inhibits the formation of the stacks. This offers a simple biophysical explanation for surfactant inhibition in adult respiratory distress syndrome and possible targets for treatment.
The relationship between a model pulmonary surfactant system and various sized nanoparticles was investigated in this study. Diplamitoylphosphatidylcholine (DPPC) is the main lipid constituent of lung surfactant and has the ability to reach very high surface pressures (around 70 mN/m) upon compression. Due to these properties it was used as a model to simulate the lung surfactant film in vitro. The first objective of this study was to investigate the relationship between DPPC and various sized nanoparticles within the subphase through surface pressure-area isotherms. The second objective was to measure the surface potential of the different preparations (conducted on a mini-Langmuir trough) and to determine if an optimal nanoparticle size exists possessing a greater affinity for the DPPC film compared to other sizes. The results from the pressure area isotherms indicate that the interaction between DPPC and the nanoparticles is stable and that the 235 nm particles may represent an optimal size. Furthermore, the results from the surface potential experiments confirm that an interaction of the nanoparticles with the monolayer exists as indicated by surface-pressure area isotherms. Any even moderate interaction between nanoparticles and lung surfactant film might reduce or increase the surface potential of the surfactant film, and this might impact the deposition of the nanoparticles or other ligands which may be positively or negatively charged drugs within the surfactant film. Thus changes in surface potential due to nanoparticle interactions have to be taken into account for future drug targeting studies using nano-sized drug carriers.
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