TiO2 nanoparticles are highly produced nanomaterials from industry and commonly found in the air we breathe, but their interactions with lung surfactants and impairing lung functions have not well understood. In this study, effects of two crystalline structures of TiO2 nanoparticles, i.e., anatase and rutile, with their various sizes, shapes, surface charges and concentrations, interacting with a single-component model of pulmonary surfactant, were studied. Nonlinear interfacial rheology was used to quantitatively distinguish effects of nanoparticles at different stages of breathing cycles. Oscillation studies which simulated the breathing cycles in different human ages showed that both crystalline structures of TiO2 nanoparticles made nanoparticles-dipalmitoyl phosphatidylcholine (DPPC) system more viscous, dissipative and irreversible during the oscillations, thus affecting the normal operation of lung surfactant. At the least concentration of nanoparticles studied, i.e., 0.01 wt%, the anatase ones significantly affected the expansion part of the cycle, whereas the rutile ones affected both expansion and compression phases. Interactions between DPPC and TiO2 nanoparticles under dynamic conditions of breathing cycles were affected by the crystalline structures and concentrations of nanoparticles and breathing conditions, with key factors including physical properties, such as sizes, shapes, and zeta potentials of nanoparticles. These results are crucial for understanding the adverse effects of nanosized pollutants in the lungs and applying drug delivery into lungs.

• Klíčová slova
• Air-liquid interface, DPPC, Lung Surfactant, Surface tension, Titanium dioxide nanoparticles,
• MeSH
• 1,2-dipalmitoylfosfatidylcholin chemie   MeSH
• lidé MeSH
• nanočástice * chemie   MeSH
• plicní surfaktanty * chemie   MeSH
• reologie MeSH
• titan * chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 1,2-dipalmitoylfosfatidylcholin MeSH
• plicní surfaktanty * MeSH
• titan * MeSH
• titanium dioxide MeSH Prohlížeč

In this study, we investigated the stability of the fully activated conformation of the orexin receptor 2 (OX2R) embedded in a pure POPC bilayer using MD simulations. Various thermodynamic ensembles (i.e., NPT, NVT, NVE, NPAT, μVT, and NPγT) were employed to explore the dynamical heterogeneity of the system in a comprehensive way. In addition, informational similarity metrics (e.g., Jensen-Shannon divergence) as well as Markov state modeling approaches were utilized to elucidate the receptor kinetics. Special attention was paid to assessing surface tension within the simulation box, particularly under NPγT conditions, where 21 nominal surface tension constants were evaluated. Our findings suggest that traditional thermodynamic ensembles such as NPT may not adequately control physical properties of the POPC membrane, impacting the plausibility of the OX2R model. In general, the performed study underscores the importance of employing the NPγT ensemble for computational investigations of membrane-embedded receptors, as it effectively maintains zero surface tension in the simulated system. These results offer valuable insights for future research aimed at understanding receptor dynamics and designing targeted therapeutics.

• MeSH
• fosfatidylcholiny chemie   MeSH
• lidé MeSH
• lipidové dvojvrstvy chemie   MeSH
• Markovovy řetězce MeSH
• orexinové receptory * chemie   metabolismus   MeSH
• povrchové napětí MeSH
• simulace molekulární dynamiky * MeSH
• termodynamika * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 1-palmitoyl-2-oleoylphosphatidylcholine MeSH Prohlížeč
• fosfatidylcholiny MeSH
• lipidové dvojvrstvy MeSH
• orexinové receptory * MeSH

The structural response of 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC)/water bilayers to addition and subsequent solvation of a small amphiphilic molecule - an anesthetic benzyl alcohol - was studied by means of solid-state NMR (2H NMR, 31P NMR) spectroscopy and low-angle X-ray diffraction. The sites of binding of this solute molecule within the bilayer were determined - the solute was shown to partition between several sites in the bilayer and the equilibrium was shown to be dynamic and dependent on the level of hydration and temperature. At the same time, it was shown that solubilization of benzyl alcohol reached a solubility limit and was terminated when the ordering profile of DMPC hydrocarbon chains adopted finite limiting values throughout the whole chain. Such findings were made probably for the first time for any lipid bilayer system and possibly have more general implications for dissolution of other small-molecule amphiphilic solutes in lipid bilayer systems other than DMPC. The limit to the hydrocarbon chain profile is probably a more general property and corresponds to the balance of intrabilayer and interbilayer forces established in combination with the elastic properties of the bilayer system that still consists of one single phase just before the solute forms an excess phase. It is not necessary to quantify the contribution of each individual intrabilayer and interbilayer force acting within such a bilayer system. A model of the dependence of surface density of lipid chains on the chain segment order parameter was also developed - an empirical mathematical model based on experimental data was derived and it was proposed to represent a relationship between intrinsic bilayer forces and bilayer deformation characteristics and might be proven to be of more general significance in the future.

• MeSH
• anestetika * chemie   MeSH
• benzylalkohol * chemie   MeSH
• difrakce rentgenového záření MeSH
• dimyristoylfosfatidylcholin chemie   MeSH
• lipidové dvojvrstvy * chemie   MeSH
• magnetická rezonanční spektroskopie MeSH
• rozpouštědla chemie   MeSH
• rozpustnost MeSH
• teplota MeSH
• voda chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• anestetika * MeSH
• benzylalkohol * MeSH
• dimyristoylfosfatidylcholin MeSH
• lipidové dvojvrstvy * MeSH
• rozpouštědla MeSH
• voda MeSH

Understanding the molecular mechanisms of pore formation is crucial for elucidating fundamental biological processes and developing therapeutic strategies, such as the design of drug delivery systems and antimicrobial agents. Although experimental methods can provide valuable information, they often lack the temporal and spatial resolution necessary to fully capture the dynamic stages of pore formation. In this study, we present two novel collective variables (CVs) designed to characterize membrane pore behavior, particularly its energetics, through molecular dynamics (MD) simulations. The first CV─termed Full-Path─effectively tracks both the nucleation and expansion phases of pore formation. The second CV─called Rapid─is tailored to accurately assess pore expansion in the limit of large pores, providing quick and reliable method for evaluating membrane line tension under various conditions. Our results clearly demonstrate that the line tension predictions from both our CVs are in excellent agreement. Moreover, these predictions align qualitatively with available experimental data. Specifically, they reflect higher line tension of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membranes containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (POPS) lipids compared to pure POPC, the decrease in line tension of POPC vesicles as the 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) content increases, and higher line tension when ionic concentration is increased. Notably, these experimental trends are accurately captured only by the all-atom CHARMM36 and prosECCo75 force fields. In contrast, the all-atom Slipids force field, along with the coarse-grained Martini 2.2, Martini 2.2 polarizable, and Martini 3 models, show varying degrees of agreement with experiments. Our developed CVs can be adapted to various MD simulation engines for studying pore formation, with potential implications in membrane biophysics. They are also applicable to simulations involving external agents, offering an efficient alternative to existing methodologies.

• MeSH
• buněčná membrána * chemie   metabolismus   MeSH
• fosfatidylcholiny chemie   MeSH
• lipidové dvojvrstvy * chemie   MeSH
• poréznost MeSH
• simulace molekulární dynamiky * MeSH
• termodynamika * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 1-palmitoyl-2-oleoylphosphatidylcholine MeSH Prohlížeč
• fosfatidylcholiny MeSH
• lipidové dvojvrstvy * MeSH

Cellular membranes are composed of lipids typically organized in a double-leaflet structure. Interactions between these two leaflets - often referred to as interleaflet coupling - play a crucial role in various cellular processes. Despite extensive study, the mechanisms governing such interactions remain incompletely understood. Here, we investigate the effects of interleaflet coupling from a specific point of view, i.e. by comparing diffusive dynamics in bilayers and monolayers, focusing on potential lipid-specific interactions between opposing leaflets. Through quantitative fluorescence microscopy techniques, we characterize lipid diffusion and mean molecular area in monolayers and bilayers composed of different lipids. Our results suggest that the observed decrease in bilayer lipid diffusion compared to monolayers depends on lipid identity. Furthermore, our analysis suggests that lipid acyl chain structure and spatial configuration at the bilayer may strongly influence interleaflet interactions and dynamics in bilayers. These findings provide insights into the role of lipid structure in mediating interleaflet coupling and underscore the need for further experimental investigations to elucidate the underlying mechanisms.

• Klíčová slova
• Bilayer, Fluorescence correlation spectroscopy, Interleaflet coupling, Lipids, Monolayer, Raster image correlation spectroscopy,
• MeSH
• buněčná membrána chemie   metabolismus   MeSH
• difuze MeSH
• fluorescenční mikroskopie MeSH
• fosfatidylcholiny chemie   MeSH
• lipidové dvojvrstvy * chemie   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• fosfatidylcholiny MeSH
• lipidové dvojvrstvy * MeSH

The transformation of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid bilayers from the gel (Lβ') to the fluid (Lα) phase involves an intermediate ripple (Pβ') phase forming a few degrees below the main transition temperature (Tm). While the exact cause of bilayer rippling is still debated, the presence of amphiphilic molecules, pH, and lipid bilayer architecture are all known to influence (pre)transition behavior. In particular, fatty acid chains interact with hydrophobic lipid tails, while the carboxylic groups simultaneously participate in proton transfer with interfacial water in the polar lipid region which is controlled by the pH of the surrounding aqueous medium. The molecular-level variations in the DPPC ripple phase in the presence of 2% palmitic acid (PA) were studied at pH levels 4.0, 7.3, and 9.1, where PA is fully protonated, partially protonated, or fully deprotonated. Bilayer thermotropic behavior was investigated by differential scanning calorimetry (DSC) and Fourier-transform infrared (FTIR) spectroscopy which agreed in their characterization of (pre)transition at pH of 9.1, but not at pH 4.0 and especially not at 7.3. Owing to the different insertion depths of protonated and deprotonated PA, along with the ability of protonated PA to undergo flip-flop in the bilayer, these two forms of PA show a different hydration pattern in the interfacial water layer. Finally, these results demonstrated the hitherto undiscovered potential of FTIR spectroscopy in the detection of the events occurring at the surface of lipid bilayers that obscure the low-cooperativity phase transition explored in this work.

• Klíčová slova
• 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid bilayers, DSC and FTIR spectroscopy, Palmitic acid (PA), Ripple phase, pH-dependent (de)protonation,
• MeSH
• 1,2-dipalmitoylfosfatidylcholin * analogy a deriváty   MeSH
• diferenciální skenovací kalorimetrie MeSH
• koncentrace vodíkových iontů MeSH
• kyselina palmitová * chemie   MeSH
• lipidové dvojvrstvy * chemie   MeSH
• molekulární struktura MeSH
• protony MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• teplota MeSH
• změna skupenství MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 1,2-dipalmitoylfosfatidylcholin * MeSH
• colfosceril palmitate MeSH Prohlížeč
• kyselina palmitová * MeSH
• lipidové dvojvrstvy * MeSH
• protony MeSH

Lipidomics and metabolomics communities comprise various informatics tools; however, software programs handling multimodal mass spectrometry (MS) data with structural annotations guided by the Lipidomics Standards Initiative are limited. Here, we provide MS-DIAL 5 for in-depth lipidome structural elucidation through electron-activated dissociation (EAD)-based tandem MS and determining their molecular localization through MS imaging (MSI) data using a species/tissue-specific lipidome database containing the predicted collision-cross section values. With the optimized EAD settings using 14 eV kinetic energy, the program correctly delineated lipid structures for 96.4% of authentic standards, among which 78.0% had the sn-, OH-, and/or C = C positions correctly assigned at concentrations exceeding 1 μM. We showcased our workflow by annotating the sn- and double-bond positions of eye-specific phosphatidylcholines containing very-long-chain polyunsaturated fatty acids (VLC-PUFAs), characterized as PC n-3-VLC-PUFA/FA. Using MSI data from the eye and n-3-VLC-PUFA-supplemented HeLa cells, we identified glycerol 3-phosphate acyltransferase as an enzyme candidate responsible for incorporating n-3 VLC-PUFAs into the sn1 position of phospholipids in mammalian cells, which was confirmed using EAD-MS/MS and recombinant proteins in a cell-free system. Therefore, the MS-DIAL 5 environment, combined with optimized MS data acquisition methods, facilitates a better understanding of lipid structures and their localization, offering insights into lipid biology.

• MeSH
• data mining * metody   MeSH
• fosfatidylcholiny metabolismus   chemie   MeSH
• HeLa buňky MeSH
• hmotnostní spektrometrie metody   MeSH
• lidé MeSH
• lipidomika * metody   MeSH
• lipidy chemie   analýza   MeSH
• metabolomika metody   MeSH
• nenasycené mastné kyseliny metabolismus   chemie   MeSH
• software MeSH
• tandemová hmotnostní spektrometrie metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fosfatidylcholiny MeSH
• lipidy MeSH
• nenasycené mastné kyseliny MeSH

The aim of this study was to analyze the functional properties of newly obtained films based on sodium alginate and lecithin with the addition of antioxidant-rich coffee extracts and to verify their potential as safe edible food packaging materials. In our study, we developed alginate-lecithin films enriched with green or roasted coffee bean extracts. The roasting process of coffee beans had a significant impact on the total phenolic content (TPC) in the studied extracts. The highest value of TPC (2697.2 mg GAE/dm3), as well as antioxidant activity (AA) (17.6 mM T/dm3), was observed for the extract of light-roasted coffee beans. Films with the addition of medium-roasted coffee extracts and baseline films had the highest tensile strength (21.21 ± 0.73 N). The addition of coffee extract improved the barrier properties of the films against UV light with a decrease in the transmittance values (200-400 nm), regardless of the type of extract added. Studies on Caco-2, HepG2 and BJ cells showed that digestated films were non-cytotoxic materials (100-0.1 μg/cm3) and had no negative effect on cell viability; an increase was noted for all cell lines, the highest after 48 h in a dose of 1 μg/cm3 for a film with medium-roasted coffee (194.43 ± 38.30) for Caco-2. The tested films at 20% digestate concentrations demonstrated the ability to reduce nitric oxide (NO) production in the RAW264.7 cell line by 25 to 60% compared to the control. Each of the tested films with coffee extracts had growth inhibitory properties towards selected species of bacteria.

• Klíčová slova
• antimicrobial activity, antioxidant activity, biopolymer-based packaging, coffee extracts, cytotoxicity, edible packaging, lecithin, nitric oxide, sodium alginate,
• MeSH
• algináty * chemie   farmakologie   MeSH
• antiflogistika * farmakologie   chemie   MeSH
• antiinfekční látky farmakologie   chemie   MeSH
• antioxidancia * farmakologie   chemie   MeSH
• buňky Hep G2 MeSH
• Caco-2 buňky MeSH
• Coffea chemie   MeSH
• jedlé filmy MeSH
• káva chemie   MeSH
• lecitiny * chemie   MeSH
• lidé MeSH
• myši MeSH
• obaly potravin metody   MeSH
• rostlinné extrakty * chemie   farmakologie   MeSH
• semena rostlinná chemie   MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• algináty * MeSH
• antiflogistika * MeSH
• antiinfekční látky MeSH
• antioxidancia * MeSH
• káva MeSH
• lecitiny * MeSH
• rostlinné extrakty * MeSH

Perforation of the outer mitochondrial membrane triggered by BAX and facilitated by its main activator cBID is a fundamental process in cell apoptosis. Here, we employ a newly designed correlative approach based on a combination of a fluorescence cross correlation binding with a calcein permeabilization assay to understand the involvement of BAX in pore formation under oxidative stress conditions. To mimic the oxidative stress, we enriched liposomal membranes by phosphatidylcholines with truncated sn-2 acyl chains terminated by a carboxyl or aldehyde moiety. Our observations revealed that oxidative stress enhances proapoptotic conditions involving accelerated pore-opening kinetics. This enhancement is achieved through increased recruitment of BAX to the membrane and facilitation of BAX membrane insertion. Despite these effects, the fundamental mechanism of pore formation remained unchanged, suggesting an all-or-none mechanism. In line with this mechanism, we demonstrated that the minimal number of BAX molecules at the membrane necessary for pore formation remains constant regardless of BAX activation by cBID or the presence of oxidized lipids. Overall, our findings give a comprehensive picture of the molecular mechanisms underlying apoptotic pore formation and highlight the selective amplifying role of oxidized lipids in triggering formation of membrane pores.

• MeSH
• apoptóza MeSH
• fluoresceiny chemie   metabolismus   MeSH
• fosfatidylcholiny chemie   metabolismus   MeSH
• lidé MeSH
• liposomy chemie   metabolismus   MeSH
• mitochondriální membrány metabolismus   MeSH
• oxidační stres * MeSH
• poréznost MeSH
• protein X asociovaný s bcl-2 * metabolismus   chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fluoresceiny MeSH
• fluorexon MeSH Prohlížeč
• fosfatidylcholiny MeSH
• liposomy MeSH
• protein X asociovaný s bcl-2 * MeSH

Lipidome perturbation occurring during meta-inflammation is associated to left ventricle (LV) remodeling though the activation of the NLRP3 inflammasome, a key regulator of chronic inflammation in obesity-related disorders. Little is known about phosphatidylcholine (PC) and phosphatidylethanolamine (PE) as DAMP-induced NLRP3 inflammasome. Our study is aimed to evaluate if a systemic reduction of PC/PE molar ratio can affect NLRP3 plasma levels in cardiovascular disease (CVD) patients with insulin resistance (IR) risk. Forty patients from IRCCS Policlinico San Donato were enrolled, and their blood samples were drawn before heart surgery. LV geometry measurements were evaluated by echocardiography and clinical data associated to IR risk were collected. PC and PE were quantified by ESI-MS/MS. Circulating NLRP3 was quantified by an ELISA assay. Our results have shown that CVD patients with IR risk presented systemic lipid impairment of PC and PE species and their ratio in plasma was inversely associated to NLRP3 levels. Interestingly, CVD patients with IR risk presented LV changes directly associated to increased levels of NLRP3 and a decrease in PC/PE ratio in plasma, highlighting the systemic effect of meta-inflammation in cardiac response. In summary, PC and PE can be considered bioactive mediators associated to both the NLRP3 and LV changes in CVD patients with IR risk.

• Klíčová slova
• Cardiac remodeling, Cardiovascular diseases (CVDs), Insulin resistance (IR) risk, NOD-like receptor family pyrin domain-containing 3 (NLRP3), Phosphatidylcholine (PC), Phosphatidylethanolamine (PE),
• MeSH
• fosfatidylcholiny * krev   MeSH
• fosfatidylethanolaminy * krev   metabolismus   MeSH
• inflamasomy * metabolismus   MeSH
• inzulinová rezistence * MeSH
• kardiovaskulární nemoci * krev   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• protein NLRP3 * metabolismus   MeSH
• remodelace komor * MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fosfatidylcholiny * MeSH
• fosfatidylethanolaminy * MeSH
• inflamasomy * MeSH
• NLRP3 protein, human MeSH Prohlížeč
• phosphatidylethanolamine MeSH Prohlížeč
• protein NLRP3 * MeSH