lipid packing Dotaz Zobrazit nápovědu
Ceramides (Cers) with ultralong (∼32-carbon) chains and ω-esterified linoleic acid, composing a subclass called omega-O-acylceramides (acylCers), are indispensable components of the skin barrier. Normal barriers typically contain acylCer concentrations of ∼10 mol%; diminished concentrations, along with altered or missing long periodicity lamellar phase (LPP), and increased permeability accompany an array of skin disorders, including atopic dermatitis, psoriasis, and ichthyoses. We developed model membranes to investigate the effects of the acylCer structure and concentration on skin lipid organization and permeability. The model membrane systems contained six to nine Cer subclasses as well as fatty acids, cholesterol, and cholesterol sulfate; acylCer content-namely, acylCers containing sphingosine (Cer EOS), dihydrosphingosine (Cer EOdS), and phytosphingosine (Cer EOP) ranged from zero to 30 mol%. Systems with normal physiologic concentrations of acylCer mixture mimicked the permeability and nanostructure of human skin lipids (with regard to LPP, chain order, and lateral packing). The models also showed that the sphingoid base in acylCer significantly affects the membrane architecture and permeability and that Cer EOP, notably, is a weaker barrier component than Cer EOS and Cer EOdS. Membranes with diminished or missing acylCers displayed some of the hallmarks of diseased skin lipid barriers (i.e., lack of LPP, less ordered lipids, less orthorhombic chain packing, and increased permeability). These results could inform the rational design of new and improved strategies for the barrier-targeted treatment of skin diseases.
The lipids in the mammalian stratum corneum (SC) adopt an unusually rigid arrangement to form a vital barrier preventing water loss and harmful environmental impacts. Just above the physiological temperature, a subset of barrier lipids undergoes a phase transition from a very tight orthorhombic to a looser hexagonal arrangement and vice versa. The purpose of this lipid transition in skin physiology is unknown. Permeability experiments on isolated human SC indicated that the transition affects the activation energy for a model compound that prefers lateral movement along lipid layers but not for water or a large polymer that would cross the SC through the pore pathway. The orthorhombic phase content of SC lipids, as determined by infrared spectroscopy, was also modulated by (de)hydration. Spontaneous rearrangement of human SC lipid monolayers into 10 nm higher multilamellar islets at 32-37 °C but not at room temperature was revealed by atomic force microscopy. Our findings add to our knowledge of fundamental skin physiology suggesting a fine temperature- and hydration-controlled switch from fluid lipids (required for lipid barrier assembly) to rigid and tightly packed lipids in the mature SC (necessary for the water and permeability barriers).
Účel studie: Cílem této pilotní studie bylo popsat změny v lipidovém metabolizmu u pacientů s akutním krvácením do gastrointestinálního traktu (GIT) a posoudit možný vliv hemodiluce a změn v procesu získávání cholesterolu (syntéza a absorpce). Materiál a metody: U dvanácti pacientů s akutním krvácením do GIT byly stanoveny hodnoty lipidového metabolizmu (celkový, LDL a HDL cholesterol, triglyceridy) v den 0, 3 a 6. Ve stejných termínech byly stanoveny hladiny ukazatelů cholesterolové syntézy (skvalen, lathosterol) a absorpce (sitosterol, kampesterol). Výsledky byly hodnoceny srovnáním s kontrolním souborem a porovnáním nemocných s cirhózou a bez postižení jater. Současně byl hodnocen vztah mezi lipidy a hodnotami hemoglobinu, hematokritu a spotřebou transfuzí. Výsledky: Hladiny celkového cholesterolu byly sníženy významně (p < 0,001), HDL a LDL nevýznamně a triglyceridy byly v normě. Hladiny lathosterolu byly sníženy signifikantně (p < 0,05), skvalenu, kampesterolu a sitosterolu nesignifikantně. Porovnání pacientů s cirhózou a bez ní přineslo statisticky významný rozdíl v hladinách cholesterolu a lathosterolu (p < 0,05). Korelace nepřinesly statisticky významné nálezy. Závěr: U pacientů s akutním krvácením do horního GITu byly prokázány změny v metabolizmu lipidů včetně alterace procesu syntézy i absorpce. Hypocholesterolemii proto nelze vysvětlit pouze krevní ztrátou. Je nutné provést další podrobnější studie.
Purpose of the study: The aim of this pilot study was to describe changes in lipid metabolism in patients with acute gastrointestinal (GI) bleeding and to assess possible influence of hemodilution and changes in the cholesterol synthesis/absorption process. Material and methods: In 12 patients with gastrointestinal bleeding, the levels of lipid metabolism (total, LDL and HDL cholesterol and triglycerides) were determined on days 0, 3 and 6. On the same days, levels of the cholesterol synthesis indexes (lathosterol, squalene) and absorption (campesterol, sitosterol) were determined. The results were evaluated in comparison with the control set, and cirrhotic and non-cirrhotic patients were compared. At the same time, correlations of lipids and haemoglobin, hematocrit levels anduse of transfusions were evaluated. Results: The patients had significantly lower levels of total cholesterol (p < 0.001). Decrease of LDL and HDL cholesterol was not significant. Concentrations of triglycerides were normal. Decrease of lathosterol was significant (p < 0.05), but decrease in squalene, campesterol and sitosterol levels was insignificant. Comparing patients with cirrhosis and without cirrhosis showed statistically significant difference in levels of cholesterol and lathosterol (p < 0.05). Correlations did not show any statistically significant findings. Conclusion: In patients with acute GI bleeding, changes is lipid metabolism including alteration of the process of synthesis and absorption were proved. Therefore, hypocholesterolemia cannot be explained by blood loss only. However, more detailed studies need to be carried out. 30. 1. 2013
- MeSH
- akutní nemoc MeSH
- časové faktory MeSH
- cholesterol * analogy a deriváty krev metabolismus MeSH
- fytosteroly krev MeSH
- gastrointestinální krvácení * krev metabolismus MeSH
- HDL-cholesterol krev metabolismus MeSH
- hematokrit MeSH
- hemodiluce MeSH
- jaterní cirhóza komplikace MeSH
- kritický stav MeSH
- LDL-cholesterol krev metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipidy MeSH
- pilotní projekty MeSH
- sitosteroly krev MeSH
- skvalen krev MeSH
- statistika jako téma MeSH
- steroly MeSH
- studie případů a kontrol MeSH
- triglyceridy krev metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
Chloroplast thylakoid membranes contain virtually all components of the energy-converting photosynthetic machinery. Their energized state, driving ATP synthesis, is enabled by the bilayer organization of the membrane. However, their most abundant lipid species is a non-bilayer-forming lipid, monogalactosyl-diacylglycerol; the role of lipid polymorphism in these membranes is poorly understood. Earlier 31P-NMR experiments revealed the coexistence of a bilayer and a non-bilayer, isotropic lipid phase in spinach thylakoids. Packing of lipid molecules, tested by fluorescence spectroscopy of the lipophilic dye, merocyanine-540 (MC540), also displayed heterogeneity. Now, our 31P-NMR experiments on spinach thylakoids uncover the presence of a bilayer and three non-bilayer lipid phases; time-resolved fluorescence spectroscopy of MC540 also reveals the presence of multiple lipidic environments. It is also shown by 31P-NMR that: (i) some lipid phases are sensitive to the osmolarity and ionic strength of the medium, (ii) a lipid phase can be modulated by catalytic hydrogenation of fatty acids and (iii) a marked increase of one of the non-bilayer phases upon lowering the pH of the medium is observed. These data provide additional experimental evidence for the polymorphism of lipid phases in thylakoids and suggest that non-bilayer phases play an active role in the structural dynamics of thylakoid membranes.
Lipid bilayer properties are quantified with a variety of arbitrary selected parameters such as molecular packing and dynamics, electrostatic potentials or permeability. In the paper we determined the effect of phloretin and 6-ketocholestanol (dipole potential modifying agents) on the membrane hydration and efficiency of the trans-membrane water flow. The dynamics of water molecules within the lipid bilayer interface was evaluated using solvent relaxation method, whereas the osmotically induced trans-membrane water flux was estimated with the stopped-flow method using the liposome shrinkage kinetics. The presence of phloretin or 6-ketocholestanol resulted in a change of both, the interfacial hydration level and osmotically driven water fluxes. Specifically, the presence of 6-ketocholestanol reduced the amount and mobility of water in the membrane interface. It also slows the osmotically induced water flow. The interfacial hydration change caused by phloretin was much smaller and the effect on osmotically induced water flow was opposite to that of 6-ketocholestanol.
- MeSH
- floretin chemie MeSH
- fluorescenční barviva chemie MeSH
- ketocholesteroly chemie MeSH
- lipidové dvojvrstvy chemie metabolismus MeSH
- liposomy chemie metabolismus MeSH
- permeabilita MeSH
- simulace molekulární dynamiky * MeSH
- voda chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The coexistence of lipid domains with different degrees of lipid packing in the plasma membrane of mammalian cells has been postulated, but direct evidence has so far been challenging to obtain because of the small size and short lifetime of these domains in live cells. Here, we use fluorescence spectral correlation spectroscopy in conjunction with a probe sensitive to the membrane environment to quantify spectral fluctuations associated with dynamics of membrane domains in live cells. With this method, we show that membrane domains are present in live COS-7 cells and have a lifetime lower bound of 5.90 and 14.69 ms for the ordered and disordered phases, respectively. Comparisons to simulations indicate that the underlying mechanism of these fluctuations is complex but qualitatively described by a combination of dye diffusion between membrane domains as well as the motion of domains within the membrane.
- MeSH
- benzoxaziny chemie MeSH
- buněčná membrána chemie MeSH
- Cercopithecus aethiops MeSH
- COS buňky MeSH
- fluorescenční spektrometrie MeSH
- kvartérní amoniové sloučeniny chemie MeSH
- membránové lipidy chemie MeSH
- viabilita buněk MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The tear film at the ocular surface is covered by a thin layer of lipids. This oily phase stabilizes the film by decreasing its surface tension and improving its viscoelastic properties. Clinically, destabilization and rupture of the tear film are related to dry eye disease and are accompanied by changes in the quality and quantity of tear film lipids. In dry eye, eye drops containing oil-in-water emulsions are used for the supplementation of lipids and surface-active components to the tear film. We explore in detail the biophysical aspects of interactions of specific surface-active compounds, cetalkonium chloride and poloxamer 188, which are present in oil-in-water emulsions, with tear lipids. The aim is to better understand the macroscopically observed eye drops-tear film interactions by rationalizing them at the molecular level. To this end, we employ a multi-scale approach combining experiments on human meibomian lipid extracts, measurements using synthetic lipid films, and in silico molecular dynamics simulations. By combining these methods, we demonstrate that the studied compounds specifically interact with the tear lipid film enhancing its structure, surfactant properties, and elasticity. The observed effects are cooperative and can be further modulated by material packing at the tear-air interface.
- MeSH
- film jako téma * MeSH
- fluorescenční mikroskopie metody MeSH
- kvartérní amoniové sloučeniny chemie MeSH
- lidé MeSH
- lipidy chemie MeSH
- mastné alkoholy chemie MeSH
- meibomské žlázky metabolismus MeSH
- poloxamer chemie MeSH
- simulace molekulární dynamiky * MeSH
- teoretické modely MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Desulfation of cholesterol sulfate (CholS) to cholesterol (Chol) is an important event in epidermal homeostasis and necessary for stratum corneum (SC) barrier function. The CholS/Chol ratio decreases during SC maturation but remains high in pathological conditions, such as X-linked ichthyosis, characterized by dry and scaly skin. The aim of this study was to characterize the influence of the CholS/Chol molar ratio on the structure, dynamics, and permeability of SC lipid model mixtures. We synthesized deuterated CholS and investigated lipid models with specifically deuterated components using 2H solid-state NMR spectroscopy at temperatures from 25°C to 80°C. Although the rigid acyl chains in ceramides and fatty acids remained essentially rigid upon variation of the CholS/Chol ratio, both sterols were increasingly fluidized in lipid models containing higher CholS concentrations. We also show the X-ray repeat distance of the lipid lamellar phase (105 Å) and the orthorhombic chain packing of the ceramide's acyl chains and long free fatty acids did not change upon the variation of the CholS content. However, the Chol phase separation visible in models with high Chol concentration disappeared at the 50:50 CholS/Chol ratio. This increased fluidity resulted in higher permeabilities to model markers of these SC models. These results reveal that a high CholS/Chol ratio fluidizes the sterol fraction and increases the permeability of the SC lipid phase while maintaining the lamellar lipid arrangement with an asymmetric sterol distribution.
Lipid nanocarriers are among the most employed systems for drug delivery purposes in several research and industrial sectors, since their favorable properties ensure broad applicability. The design and characterization of these nanosystems are of paramount importance to obtain controlled outcome, since the supramolecular structure and molecular interactions deeply impact the functionality of the resulting aggregates. The choice of the most appropriate formulation for the target of interest relies on in-depth physico-chemical characterization in order to optimize stability, loading rates and sustained release. Several supramolecular architectures suited for carrier development can be obtained from lipid building blocks, by varying lipid composition and packing parameter. In particular, cubosome and liposome aggregates are often used as drug vectors thanks to their high cargo capability and biocompatibility. Moreover, the possibility to employ lipids from natural sources i.e. biomasses to prepare nanosystems makes them especially attractive. In this work, two aggregate types were characterized and compared as drug vectors for poorly water-soluble antioxidants, particularly curcumin and two adjuvants (i.e. tocopherol and piperine). The nanovectors were obtained by extracting lipids from algal biomasses with different lipid composition, and characterized by advanced structural (DLS, SAXS, Cryo-TEM) techniques, spectroscopy (NMR) and calorimetry (ITC). Finally, the structural stability of both aggregate types was evaluated.
