[Show abstract][Hide abstract] ABSTRACT: 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.
Full-text · Article · Aug 2007 · Biophysical Journal
[Show abstract][Hide abstract] ABSTRACT: We investigate the growth of octadecylphosphonic acid (OPA) self-assembly molecules prepared by physical vapour deposition (PVD) on mica and highly oriented pyrolytic graphite (HOPG) under ultrahigh-vacuum conditions. On samples prepared by immersion from diluted solution on mica self-assembled monolayers are formed, whereas by PVD and subsequent annealing we observe the formation of almost perfect self-assembled bilayers slightly tilted with respect to the surface normal. On the non-polar surface of HOPG, the vapour-deposited molecules adsorb in bilayers parallel to the surface, similar to the films produced by spread coating (Fontes and Neves 2005 Langmuir 21 11113). On all samples we deduce the molecular ordering by means of noncontact atomic force microscopy; on HOPG, even submolecular resolution is obtained. A comparison of our vapour-deposited films with samples prepared by other techniques mentioned in the literature demonstrates that PVD yields excellent film quality, and in many applications might be preferred due to its clean, solution-free environment and the possibility for exact dosage, e.g. for multilayer formation with a defined thickness.
[Show abstract][Hide abstract] ABSTRACT: Pulmonary surfactant is a mixed lipid protein substance of defined composition that self-assembles at the air-lung interface into a molecular film and thus reduces the interfacial tension to close to zero. A very low surface tension is required for maintaining the alveolar structure. The pulmonary surfactant film is also the first barrier for airborne particles entering the lung upon breathing. We explored by frequency modulation Kelvin probe force microscopy (FM-KPFM) the structure and local electrical surface potential of bovine lipid extract surfactant (BLES) films. BLES is a clinically used surfactant replacement and here served as a realistic model surfactant system. The films were distinguished by a pattern of molecular monolayer areas, separated by patches of lipid bilayer stacks. The stacks were at positive electrical potential with respect to the surrounding monolayer areas. We propose a particular molecular arrangement of the lipids and proteins in the film to explain the topographic and surface potential maps. We also discuss how this locally variable surface potential may influence the retention of charged or polar airborne particles in the lung.