Pulmonary surfactant is a complex mixture of lipids and proteins lining the interior of the alveoli, and constitutes the first barrier to both oxygen and pathogens as they progress toward blood circulation. Despite decades of study, the behavior of the pulmonary surfactant at the molecular scale is poorly understood, which hinders the development of effective surfactant replacement therapies, useful in the treatment of several lung-related diseases. In this work, we combined all-atom molecular dynamics simulations, Langmuir trough measurements, and AFM imaging to study synthetic four-component lipid monolayers designed to model protein-free pulmonary surfactant. We characterized the structural and dynamic properties of the monolayers with a special focus on lateral heterogeneity. Remarkably, simulations reproduce almost quantitatively the experimental data on pressure-area isotherms and the presence of lateral heterogeneities highlighted by AFM. Quite surprisingly, the pressure-area isotherms do not show a plateau region, despite the presence of liquid-condensed nanometer-sized domains at surface pressures larger than 20 mN/m. In the simulations, the liquid-condensed domains were small and transient, but they did not coalesce to yield a separate phase. They were only slightly enriched in DPPC and cholesterol, and their chemical composition remained very similar to the overall composition of the monolayer membrane. Instead, they differed from liquid-expanded regions in terms of membrane thickness (in agreement with AFM data), diffusion rates, as well as acyl chain packing and orientation. We hypothesize that such lateral heterogeneities are crucial for lung surfactant function, as they allow both efficient packing, to achieve low surface tension, and sufficient fluidity, critical for rapid adsorption to the air–liquid interface during the breathing cycle.
TiO is proposed here for the first time as a substrate for neural prostheses that involve electrical stimulation. Several characteristics make TiO an attractive material: Its electrochemical behaviour as an insulator prevents surface changes during stimulation. Hydration creates -OH groups at the surface, which aid cell adhesion by interaction with inorganic ions and macromolecules in cell membranes. Its ability to neutralize reactive oxygen and nitrogen species that trigger inflammatory processes confers biocompatibility properties in dark conditions. Here, physicochemical characterization of TiO samples and their surfaces was carried out by X-ray diffraction, X-ray photoelectronic emission spectroscopy, scanning electron microscopy, atomic force microscopy and by contact angle measurements. Its properties were related to the growth parameters and morphology of amphibian spinal neurons cultured on TiO samples. Neurons adhered to and extended neurites directly on TiO surfaces without pre-coating with adhesive molecules, indicating that the material permits intimate neuron-surface interactions. On TiO surfaces the distal tips of each extending neurite and the neurite shafts themselves showed more complex filopodial morphology compared with control cultures on glass. Importantly, the ability of TiO to support neuron growth during electric field exposure was also tested. The extent of growth and the degree of neurite orientation relative to the electric field on TiO approximated that on glass control substrates. Collectively, the data suggest that TiO materials support neuron growth and that they have potential utility for neural prosthetic applications incorporating electric field stimulation, especially where intimate contact of neurons with the material is beneficial.
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