Charge scaling has proven to be an efficient way to account in a mean-field manner for electronic polarization by aqueous ions in force field molecular dynamics simulations. However, commonly used water models with dielectric constants over 50 are not consistent with this approach leading to "overscaling", i.e., generally too weak ion-ion interactions. Here, we build water models fully compatible with charge scaling, i.e., having the correct low-frequency dielectric constant of about 45. To this end, we employ advanced optimization and machine learning schemes in order to explore the vast parameter space of four-site water models efficiently. As an a priori unwarranted positive result, we find a sizable range of force field parameters that satisfy the above dielectric constant constraint providing at the same time accuracy with respect to experimental data comparable with the best existing four-site water models such as TIP4P/2005, TIP4P-FB, or OPC. The present results thus open the way to the development of a consistent charge scaling force field for modeling ions in aqueous solutions.

• Publikační typ
• časopisecké články 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

Biomembranes, important building blocks of living organisms, are often exposed to large local fluctuations of pH and ionic strength. To capture changes in the membrane organization under such harsh conditions, we investigated the mobility and hydration of zwitterionic and anionic lipid bilayers upon elevated H3O+ and Ca2+ content by the time-dependent fluorescence shift (TDFS) technique. While the zwitterionic bilayers remain inert to lower pH and increased calcium concentrations, anionic membranes are responsive. Specifically, both bilayers enriched in phosphatidylserine (PS) and phosphatidylglycerol (PG) become dehydrated and rigidified at pH 4.0 compared to at pH 7.0. However, their reaction to the gradual Ca2+ increase in the acidic environment differs. While the PG bilayers exhibit strong rehydration and mild loosening of the carbonyl region, restoring membrane properties to those observed at pH 7.0, the PS bilayers remain dehydrated with minor bilayer stiffening. Molecular dynamics (MD) simulations support the strong binding of H3O+ to both PS and PG. Compared to PS, PG exhibits a weaker binding of Ca2+ also at a low pH.

• Klíčová slova
• Laurdan, anionic lipids, calcium, headgroup mobility, headgroup organization, lipid hydration, molecular dynamics, phospholipid bilayer, proton, time dependent fluorescence shift,
• MeSH
• fosfatidylseriny MeSH
• ionty MeSH
• lipidové dvojvrstvy * chemie   MeSH
• protony * MeSH
• simulace molekulární dynamiky MeSH
• vápník chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fosfatidylseriny MeSH
• ionty MeSH
• lipidové dvojvrstvy * MeSH
• protony * MeSH
• vápník MeSH