| 1. |
- Ermilova, Inna, 1983, et al.
(författare)
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Ionizable lipids penetrate phospholipid bilayers with high phase transition temperatures: perspectives from free energy calculations
- 2023
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Ingår i: Chemistry and Physics of Lipids. - : Elsevier BV. - 0009-3084 .- 1873-2941. ; 253
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Tidskriftsartikel (refereegranskat)abstract
- The efficacies of modern gene-therapies strongly depend on their contents. At the same time the most potent formulations might not contain the best compounds. In this work we investigated the effect of phospholipids and their saturation on the binding ability of (6Z,9Z,28Z,31Z)-heptatriacont-6,9,28,31-tetraene-19-yl 4-(dimethylamino) butanoate (DLin-MC3-DMA) to model membranes at the neutral pH. We discovered that DLin-MC3-DMA has affinity to the most saturated monocomponent lipid bilayer 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and an aversion to the unsaturated one 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). The preference to a certain membrane was also well-correlated to the phase transition temperatures of phospholipid bilayers, and to their structural and dynamical properties. Additionally, in the case of the presence of DLin-MC3-DMA in the membrane with DOPC the ionizable lipid penetrated it, which indicates possible synergistic effects. Comparisons with other ionizable lipids were performed using a model lipid bilayer of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC). Particularly, the lipids heptadecan-9-yl 8-[2-hydroxyethyl-(6-oxo-6-undecoxyhexyl)amino]octanoate (SM-102) and [(4-hydroxybutyl) azanediyl] di(hexane-6,1-diyl) bis(2-hexyldecanoate) (ALC-0315) from modern mRNA-vaccines against COVID-19 were investigated and force fields parameters were derived for those new lipids. It was discovered that ALC-0315 binds strongest to the membrane, while DLin-MC3-DMA is not able to reside in the bilayer center. The ability to penetrate the membrane POPC by SM-102 and ALC-0315 can be related to their saturation, comparing to DLin-MC3-DMA.
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| 2. |
- Luchini, Alessandra, et al.
(författare)
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Effect of ergosterol on the interlamellar spacing of deuterated yeast phospholipid multilayers
- 2020
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Ingår i: Chemistry and Physics of Lipids. - : Elsevier BV. - 0009-3084. ; 227
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Tidskriftsartikel (refereegranskat)abstract
- Sterols regulate several physico-chemical properties of biological membranes that are considered to be linked to function. Ergosterol is the main sterol molecule found in the cell membranes of yeasts and other fungi. Like the cholesterol found in mammalian cells, ergosterol has been proposed to have an ordering and condensing effect on saturated phospholipid membranes. The effects of cholesterol have been investigated extensively and result in an increase in the membrane thickness and the lipid acyl chain order. Less information is available on the effects of ergosterol on phospholipid membranes. Neutron Diffraction (ND) was used to characterize the effect of ergosterol on lipid multilayers prepared with deuterated natural phospholipids extracted from the yeast Pichia pastoris. The data show that the effect of ergosterol on membranes prepared from the natural phospholipid extract rich in unsaturated acyl chains, differs from what has been observed previously in membranes rich in saturated phospholipids. In contrast to cholesterol in synthetic phospholipid membranes, the presence of ergosterol up to 30 mol % in yeast phospholipid membranes only slightly altered the multilayer structure. In particular, only a small decrease in the multilayer d-spacing was observed as function of increasing ergosterol concentrations. This result highlights the need for further investigation to elucidate the effects of ergosterol in biological lipid mixtures.
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| 3. |
- Qamhieh, Khawla, et al.
(författare)
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Electrostatic interactions between cationic dendrimers and anionic model biomembrane
- 2022
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Ingår i: Chemistry and Physics of Lipids. - : Elsevier BV. - 0009-3084. ; 246
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Tidskriftsartikel (refereegranskat)abstract
- The electrostatic interactions between cationic poly(amidoamine) (PAMAM) dendrimers of different generations, G3, G4, and G6, with net anionic model biomembranes have been predicted by adopting an analytical model based on two dissimilar soft spheres. The influence of bilayer surface charge density, ionic strength, pH, temperature, membrane softness (modeled as changes in bilayer thickness), and dendrimer generation on the attractive interaction was investigated. The attraction was found to decrease with increasing salt concentration, dendrimer charge, and thickness (or softness) of the membrane. On the other hand, the attraction increased with the surface charge density of the membrane, and the size of dendrimer generation. In fact, the attraction was found to be much larger for large generations, like G6 dendrimer that have a higher charge, than it is with small ones like G3 and G4 dendrimers. These results have implications for the use of PAMAM dendrimers as potential gene transfection vectors.
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| 4. |
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| 5. |
- Sandrino, B., et al.
(författare)
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The prion fragment PrP106-127 adopts a secondary structure typical of aggregated fibrils in langmuir monolayers of brain lipid extract
- 2020
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Ingår i: Chemistry and Physics of Lipids. - : Elsevier BV. - 0009-3084. ; 230
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Tidskriftsartikel (refereegranskat)abstract
- Understanding protein aggregation is essential to unveil molecular mechanisms associated with neurodegenerative diseases such as Alzheimer's, Huntington's and spongiform encephalopathy, particularly to determine the role of interaction with cell membranes. In this study, we employ Langmuir monolayers as cell membrane models to mimic interaction with the peptide KTNMHKHMAGAAAAGAVVGGLG−OH, a fragment from the human prion protein including residues 106−127, believed to be involved in protein aggregation. Using in situ polarization-modulated infrared reflection adsorption spectroscopy (PM-IRRAS) for Langmuir monolayers and FTIR for solid films, we found that PrP106−127 adopts mainly β-sheets, random coils and β-turns in Langmuir monolayers and in Langmuir-Blodgett (LB) and cast films. This also applies to monolayers and solid films made with PrP106−127 and a brain total lipid extract (BTLE). In contrast, some α-helices are observed in the secondary structure of PrP106−127 in monolayers, and especially in solid films, of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). In summary, in a model representing brain cells (BTLE), the secondary structure of PrP106−127 is typical of fiber aggregates, while aggregation is unlikely if PrP106−127 interacts with a membrane model (DOPC) characteristic of mammalian cells.
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