Additives in vaping products, such as flavors, preservatives, or thickening agents, are commonly used to enhance user experience. Among these, Vitamin E acetate (VEA) was initially thought to be harmless but has been implicated as the primary cause of e-cigarette or vaping product use-associated lung injury, a serious lung disease. In our study, VEA serves as a proxy for other e-cigarette additives. To explore its harmful effects, we developed an exposure system to subject a pulmonary surfactant (PSurf) model to VEA-rich vapor. Through detailed analysis and atomic-level simulations, we found that VEA tends to cluster into aggregates on the PSurf surface, inducing deformations and weakening its essential elastic properties, critical for respiratory cycle function. Apart from VEA, our experiments also indicate that propylene glycol and vegetable glycerin, widely used in e-liquid mixtures, or their thermal decomposition products, alter surfactant properties. This research provides molecular-level insights into the detrimental impacts of vaping product additives on lung health.

• Klíčová slova
• EVALI, Lung surfactant, Molecular dynamics simulation, Pulmonary surfactant, Vaping-associated pulmonary injury,
• MeSH
• acetáty analýza   chemie   MeSH
• biologické modely MeSH
• lidé MeSH
• plicní surfaktanty * chemie   MeSH
• propylenglykol chemie   MeSH
• systémy dodávající nikotin elektronicky * MeSH
• vaping * škodlivé účinky   MeSH
• vitamin E * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetáty MeSH
• plicní surfaktanty * MeSH
• propylenglykol MeSH
• vitamin E * MeSH

Over the past decade, there has been a significant rise in the use of vaping devices, particularly among adolescents, raising concerns for effects on respiratory health. Pressingly, many recent vaping-related lung injuries are unexplained by current knowledge, and the overall implications of vaping for respiratory health are poorly understood. This study investigates the effect of hydrophobic vaping liquid chemicals on the pulmonary surfactant biophysical function. We focus on the commonly used flavoring benzaldehyde and its vaping byproduct, benzaldehyde propylene glycol acetal. The study involves rigorous testing of the surfactant biophysical function in Langmuir trough and constrained sessile drop surfactometer experiments with both protein-free synthetic surfactant and hydrophobic protein-containing clinical surfactant models. The study reveals that exposure to these vaping chemicals significantly interferes with the synthetic and clinical surfactant biophysical function. Further atomistic simulations reveal preferential interactions with SP-B and SP-C surfactant proteins. Additionally, data show surfactant lipid-vaping chemical interactions and suggest significant transfer of vaping chemicals to the experimental subphase, indicating a toxicological mechanism for the alveolar epithelium. Our study, therefore, reveals novel mechanisms for the inhalational toxicity of vaping. This highlights the need to reassess the safety of vaping liquids for respiratory health, particularly the use of aldehyde chemicals as vaping flavorings.

• Klíčová slova
• e-cigarettes, exposure and human health, inhalation toxicology, lung surfactant, mechanistic toxicology, vaping,
• MeSH
• aldehydy MeSH
• benzaldehydy MeSH
• chuťové esence MeSH
• lidé MeSH
• mladiství MeSH
• plicní surfaktanty * MeSH
• povrchově aktivní látky MeSH
• systémy dodávající nikotin elektronicky * MeSH
• vaping * MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aldehydy MeSH
• benzaldehydy MeSH
• chuťové esence MeSH
• plicní surfaktanty * MeSH
• povrchově aktivní látky MeSH

Ethylenediaminetetraacetic acid (EDTA) is frequently used in lipid experiments to remove redundant ions, such as Ca2+, from the sample solution. In this work, combining molecular dynamics (MD) simulations and Langmuir monolayer experiments, we show that on top of the expected Ca2+ depletion, EDTA anions themselves bind to phosphatidylcholine (PC) monolayers. This binding, originating from EDTA interaction with choline groups of PC lipids, leads to the adsorption of EDTA anions at the monolayer surface and concentration-dependent changes in surface pressure as measured by monolayer experiments and explained by MD simulations. This surprising observation emphasizes that lipid experiments carried out using EDTA-containing solutions, especially of high concentrations, must be interpreted very carefully due to potential interfering interactions of EDTA with lipids and other biomolecules involved in the experiment, e.g., cationic peptides, that may alter membrane-binding affinities of studied compounds.

• MeSH
• EDTA MeSH
• fosfatidylcholiny * chemie   MeSH
• ionty MeSH
• membrány umělé * MeSH
• simulace molekulární dynamiky MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• EDTA MeSH
• fosfatidylcholiny * MeSH
• ionty MeSH
• membrány umělé * MeSH

The lining of the alveoli is covered by pulmonary surfactant, a complex mixture of surface-active lipids and proteins that enables efficient gas exchange between inhaled air and the circulation. Despite decades of advancements in the study of the pulmonary surfactant, the molecular scale behavior of the surfactant and the inherent role of the number of different lipids and proteins in surfactant behavior are not fully understood. The most important proteins in this complex system are the surfactant proteins SP-B and SP-C. Given this, in this work we performed nonequilibrium all-atom molecular dynamics simulations to study the interplay of SP-B and SP-C with multicomponent lipid monolayers mimicking the pulmonary surfactant in composition. The simulations were complemented by z-scan fluorescence correlation spectroscopy and atomic force microscopy measurements. Our state-of-the-art simulation model reproduces experimental pressure-area isotherms and lateral diffusion coefficients. In agreement with previous research, the inclusion of either SP-B and SP-C increases surface pressure, and our simulations provide a molecular scale explanation for this effect: The proteins display preferential lipid interactions with phosphatidylglycerol, they reside predominantly in the lipid acyl chain region, and they partition into the liquid expanded phase or even induce it in an otherwise packed monolayer. The latter effect is also visible in our atomic force microscopy images. The research done contributes to a better understanding of the roles of specific lipids and proteins in surfactant function, thus helping to develop better synthetic products for surfactant replacement therapy used in the treatment of many fatal lung-related injuries and diseases.

• MeSH
• biofyzikální jevy MeSH
• fosfolipidy chemie   MeSH
• plicní surfaktanty * chemie   MeSH
• povrchově aktivní látky MeSH
• povrchové vlastnosti MeSH
• protein B asociovaný s plicním surfaktantem chemie   MeSH
• protein C asociovaný s plicním surfaktantem chemie   MeSH
• proteiny MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fosfolipidy MeSH
• plicní surfaktanty * MeSH
• povrchově aktivní látky MeSH
• protein B asociovaný s plicním surfaktantem MeSH
• protein C asociovaný s plicním surfaktantem MeSH
• proteiny MeSH

Lipid monolayers provide our lungs and eyes their functionality and serve as proxy systems in biomembrane research. Therefore, lipid monolayers have been studied intensively including using molecular dynamics simulations, which are able to probe their lateral structure and interactions with, e.g., pharmaceuticals or nanoparticles. However, such simulations have struggled in describing the forces at the air-water interface. Particularly, the surface tension of water and long-range van der Waals interactions have been considered critical, but their importance in monolayer simulations has been evaluated only separately. Here, we combine the recent C36/LJ-PME lipid force field that includes long-range van der Waals forces with water models that reproduce experimental surface tensions to elucidate the importance of these contributions in monolayer simulations. Our results suggest that a water model with correct surface tension is necessary to reproduce experimental surface pressure-area isotherms and monolayer phase behavior. The latter includes the liquid expanded and liquid condensed phases, their coexistence, and the opening of pores at the correct area per lipid upon expansion. Despite these improvements of the C36/LJ-PME with certain water models, the standard cutoff-based CHARMM36 lipid model with the 4-point OPC water model still provides the best agreement with experiments. Our results emphasize the importance of using high-quality water models in applications and parameter development in molecular dynamics simulations of biomolecules.

• MeSH
• lipidy MeSH
• povrchové napětí MeSH
• simulace molekulární dynamiky * MeSH
• voda * chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• lipidy MeSH
• voda * MeSH

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.

• Klíčová slova
• atomic force microscopy, heterogeneity, lipid monolayer, membrane domain, molecular dynamics simulation, pressure-area isotherm, pulmonary surfactant,
• Publikační typ
• časopisecké články MeSH

Dry eye syndrome (DES), one of the most common ophthalmological diseases, is typically caused by excessive evaporation of tear fluid from the ocular surface. Excessive evaporation is linked to impaired function of the tear film lipid layer (TFLL) that covers the aqueous tear film. The principles of the evaporation resistance of the TFLL have remained unknown, however. We combined atomistic simulations with Brewster angle microscopy and surface potential experiments to explore the organization and evaporation resistance of films composed of wax esters, one of the main components of the TFLL. The results provide evidence that the evaporation resistance of the TFLL is based on crystalline-state layers of wax esters and that the evaporation rate is determined by defects in the TFLL and its coverage on the ocular surface. On the basis of the results, uncovering the nonequilibrium spreading and crystallization of TFLL films has potential to reveal new means of treating DES.

• Publikační typ
• časopisecké články MeSH

Conformational fluctuations and rotational tumbling of proteins can be experimentally accessed with nuclear spin relaxation experiments. However, interpretation of molecular dynamics from the experimental data is often complicated, especially for molecules with anisotropic shape. Here, we apply classical molecular dynamics simulations to interpret the conformational fluctuations and rotational tumbling of proteins with arbitrarily anisotropic shape. The direct calculation of spin relaxation times from simulation data did not reproduce the experimental data. This was successfully corrected by scaling the overall rotational diffusion coefficients around the protein inertia axes with a constant factor. The achieved good agreement with experiments allowed the interpretation of the internal and overall dynamics of proteins with significantly anisotropic shape. The overall rotational diffusion was found to be Brownian, having only a short subdiffusive region below 0.12 ns. The presented methodology can be applied to interpret rotational dynamics and conformation fluctuations of proteins with arbitrary anisotropic shape. However, a water model with more realistic dynamical properties is probably required for intrinsically disordered proteins.

• MeSH
• bakteriální proteiny chemie   metabolismus   MeSH
• Helicobacter pylori metabolismus   MeSH
• izotopy dusíku chemie   MeSH
• membránové proteiny chemie   metabolismus   MeSH
• proteinové domény MeSH
• simulace molekulární dynamiky * MeSH
• spinové značení MeSH
• vnitřně neuspořádané proteiny chemie   metabolismus   MeSH
• voda chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bakteriální proteiny MeSH
• izotopy dusíku MeSH
• membránové proteiny MeSH
• Nitrogen-15 MeSH Prohlížeč
• spinové značení MeSH
• tonB protein, Bacteria MeSH Prohlížeč
• vnitřně neuspořádané proteiny MeSH
• voda MeSH