We have performed Molecular Dynamics simulations of ectoine, hydroxyectoine and urea in explicit solvent. Special attention has been spent on the local surrounding structure of water molecules. Our results indicate that ectoine and hydroxyectoine are able to accumulate more water molecules than urea by a pronounced ordering due to hydrogen bonds. We have validated that the charging of the molecules is of main importance resulting in a well defined hydration sphere. The influence of a varying salt concentration is also investigated. Finally we present experimental results of a DPPC monolayer phase transition that validate our numerical findings.

One of the most important functions of the lung surfactant monolayer is to form the first line of defence against inhaled aerosols such as nanoparticles (NPs), which remains largely unexplored. We report here, for the first time, the interaction of polyorganosiloxane NPs (AmorSil20: 22 nm in diameter) with lipid monolayers characteristic of alveolar surfactant. To enable a better understanding, the current knowledge about an established model surface film that mimics the surface properties of the lung is reviewed and major results originating from our group are summarized. The pure lipid components dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylglycerol have been used to study the biophysical behaviour of their monolayer films spread at the air -water interface in the presence of NPs. Film balance measurements combined with video-enhanced fluorescence microscopy have been used to investigate the formation of domain structures and the changes in the surface pattern induced by NPs. We are able to show that NPs are incorporated into lipid monolayers with a clear preference for defect structures at the fluid -crystalline interface leading to a considerable monolayer expansion and fluidization. NPs remain at the air-water interface probably by coating themselves with lipids in a self-assembly process, thereby exhibiting hydrophobic surface properties. We also show that the domain structure in lipid layers containing surfactant protein C, which is potentially responsible for the proper functioning of surfactant material, is considerably affected by NPs.

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The pulmonary surfactant film spanning the inner alveolar surface prevents alveolar collapse during the end-exhalation and reduces the work of breathing. Nanoparticles (NPs) present in the atmosphere or nanocarriers targeted through the pulmonary route for medical purposes challenge this biological barrier. During interaction with or passage of NPs through the alveolar surfactant, the biophysical functioning of the film may be altered. However, experimental evidence showing detailed biophysical interaction of NPs with the pulmonary surfactant film are scant. In this study, we have investigated the impact of a hydrophobic polyorganosiloxane (AmOrSil20) NPs on the integrity as well as on the structural organization of the model pulmonary surfactant film. Primarily, scanning force microscopic techniques and electron microscopy have been used to visualize the topology as well as to characterize the localization of nanoparticles within the compressed pulmonary surfactant film. We could show that the NPs partition in the fluid phase of the compressed film at lower surface pressure, and at higher surface pressure, such NPs interact extensively with the surface-associated structures. Major amounts of NPs are retained at the interface and are released slowly into the aqueous subphase during repeated compression/expansion cycles. Further, the process of vesicle insertion into the interfacial film was observed to slow down with increasing NP concentrations. The hydrophobic AmOrSil20 NPs up to a given concentration do not substantially affect the structural organization and functioning of pulmonary surfactant film; however, such NPs do show drastic impacts at higher concentrations.

The alveolar lung surfactant (LS) is a complex lipid protein mixture that forms an interfacial monolayer reducing the surface tension to near zero values and thus preventing the lungs from collapse. Due to the expanding field of nanotechnology and the corresponding unavoidable exposure of human beings from the air, it is crucial to study the potential effects of nanoparticles (NPs) on the structural organization of the lung surfactant system. In the present study, we investigated both, the domain structure in pure DPPC monolayers as well as in lung surfactant model systems. In the pure lipid system we found that two different sized hydrophobic polymeric nanoparticles with diameter of ~12 nm and ~136 nm have contrasting effect on the functional and structural behavior. The small nanoparticles inserted into fluid domains at the LE-LC phase transition are not visibly disturbing the phase transition but disrupting the domain morphology of the LE phase. The large nanoparticles led to an expanded isotherm and to a significant decrease in the line tension and thus to a drastic disruption of the domain structures at a much lower number of nanoparticles with respect to the lipid. The surface activity of the model LS films again showed drastic variations due to presence of different sized NPs illustrated by the film balance isotherms and the atomic force microscopy. AFM revealed laterally profuse multilayer protrusion formation on compression but only in the presence of 136 nm sized nanoparticles. Moreover we investigated the vesicle insertion process into a preformed monolayer. A severe inhibition was observed only in the presence of ~136 nm NPs compared to minor effects in the presence of ~12 nm NPs. Our study clearly shows that the size of the nanoparticles made of the same material determines the interaction with biological membranes.