Differential Dynamic and Structural Behavior of Lipid-Cholesterol Domains in Model Membranes

Aguilar, Luís Fuentes; Pino, José A.; Soto-Arriaza, Marco; Cuevas, Francisco; Sánchez, Susana A.; Sotomayor, Carlos P.

doi:10.1371/journal.pone.0040254

Cited by 46 publications

(39 citation statements)

References 43 publications

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“…In general, increasing the cholesterol concentration increased water penetration, likely due to greater disorder. This pattern correlates with similar results obtained in a series of studies from our group 38 . Regarding fusion, the % mixing and % leakage were studied.…”

Section: Discussionsupporting

confidence: 92%

Effect of Hydration and Packing Order on Large Unilamellar Vesicle Fusion: The Role of Cholesterol

Cuevas

Valle

Aguilar

2017

J. Chil. Chem. Soc.

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Several studies examining vesicle fusion have been reported in last decades and have established a number of factors favoring the process of vesicle fusion. To determine whether variations to the physicochemical properties of the membrane affect the process of vesicle fusion, we worked with binary and ternary mixtures of large unilamellar vesicles (LUVs). The selected binary models were dioleoyl phosphocholine-cholesterol (DOPC-chol) and disteraroyl phosphocholine-cholesterol (DSPC-chol), and the tertiary mixtures were phosphatidylcholine-phsophatidylethanolamine-cholesterol (PC-PE-Chol); phosphatidylcholine-sphingomyelincholesterol (PC-SM-Chol); and phosphatidylcholine-phosphatidylserine-cholesterol (PC-PS-Chol). For all these models, the effect of cholesterol content on the lamella physicochemical properties was determined using 1,6-diphenyl-1,3,5-hexatriene (DPH) anisotropy, generalized polarization of 2-dimethylamino-6-lauroylnaphthalene (Laurdan), and DPH fluorescence lifetime. To determine whether fusion of these vesicles varied according to lipid composition, the % mixing content and the % leakage were determined. Examining membrane incorporation using fluorescence steady-state and time-resolved probe assays in the models indicated that cholesterol content affected packing order and lamellar hydration. In most of the models, nonmonotonic variations were observed for these parameters, and these variations could be interpreted as increases in the proportion of ordered microdomains. When the proportion of these domains is higher, the packing order increases, and the lamellar water decrease. Similarly, the % mixing, which was assessed as a fusion parameter, also exhibited nonmonotonic behavior, indicating that the fusion process is enhanced at these concentrations of cholesterol. However, DSPC vesicles do not merge, so more than the presence of microdomains is required to stabilize fusion.

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Section: Discussionsupporting

confidence: 92%

Effect of Hydration and Packing Order on Large Unilamellar Vesicle Fusion: The Role of Cholesterol

Cuevas

Valle

Aguilar

2017

J. Chil. Chem. Soc.

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“…Although tricky due to the very high proportion of ordered phase, a granulometric approach reveals the formation of very large L o domains, with about 15% of L o phase present within domains above 2 M size. Altogether, our results propose the ability of GIPC and DPPC to increase membrane order level, similarly as observed previously with SM and DPPC (83), and also to promote L o domain aggregation. Moreover, a synergy is observed when GUVs are supplemented with the two lipid species together, and the strongest enhancement is seen when saturated and unsaturated PC, free and conjugated sterols, and sphingolipids are all represented.…”

Section: Journal Of Biological Chemistrysupporting

confidence: 90%

“…3), even in the absence of DPPC (Fig. 7), mimicking the SM-cholesterol effect (83). In the mammalian model, lateral partitioning of L o and L d phases is thus explained by a preferential interaction of sphingolipids with cholesterol over phospholipids (22), probably due to better shielding from water by the SM headgroup.…”

Section: Free and Conjugated Phytosterols Exhibit Various Abilities Tmentioning

confidence: 77%

“…The DOPC (T m ϭ Ϫ20°C)/DPPC (T m ϭ 41°C) lipid mixture, which has been widely used in the literature to characterize the physical properties of the membrane model system (11,14,83,108,109), exhibits, at temperatures below 45°C, an L o and L d phase coexistence (83). Performing our experiments at 22°C and minimizing temperature fluctuations, we actually favored a long time equilibrium formation of L o and L d phase separation, allowing us to focus our study on the structuring effect of plant lipid on L o and L d phase partitioning.…”

Section: Free and Conjugated Phytosterols Exhibit Various Abilities Tmentioning

confidence: 99%

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Differential Effect of Plant Lipids on Membrane Organization

Grosjean

Mongrand

Beney

et al. 2015

Journal of Biological Chemistry

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Background: The effect of the wide variety of plant lipids on membrane organization is still poorly understood. Results: The local amounts of phytosphingolipids and free and conjugated phytosterols control the relative proportion and spatial distribution of ordered domains. Conclusion: Plant lipids differently modulate, alone or in combination, membrane heterogeneity. Significance: Our results highlight how plant lipid diversity might drive the plasma membrane subcompartmentalization.

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“…Two distinct fluorescent dyes (LAURDAN and NR) were used to characterize changes in the fluidity of plasma membrane of the cells affected by the expanded polyglutamine protein. LAURDAN in particular has been well characterized in the literature and shown to be sensitive to the lipid order phases due to the lipid composition and the amount of cholesterol present in the membranes 42 , 43 . The shift we observed in membrane fluidity measured in the HD cells when expanded polyQ was expressed may reflect depletion of the cholesterol on the membrane 44 , 45 .…”

Section: Discussionmentioning

confidence: 99%

Alteration in Fluidity of Cell Plasma Membrane in Huntington Disease Revealed by Spectral Phasor Analysis

Sameni

Malacrida

Tan

et al. 2018

Sci Rep

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Huntington disease (HD) is a late-onset genetic neurodegenerative disorder caused by expansion of cytosine-adenine-guanine (CAG) trinucleotide in the exon 1 of the gene encoding the polyglutamine (polyQ). It has been shown that protein degradation and lipid metabolism is altered in HD. In many neurodegenerative disorders, impaired lipid homeostasis is one of the early events in the disease onset. Yet, little is known about how mutant huntingtin may affect phospholipids membrane fluidity. Here, we investigated how membrane fluidity in the living cells (differentiated PC12 and HEK293 cell lines) are affected using a hyperspectral imaging of widely used probes, LAURDAN. Using phasor approach, we characterized the fluorescence of LAURDAN that is sensitive to the polarity of the immediate environment. LAURDAN is affected by the physical order of phospholipids (lipid order) and reports the membrane fluidity. We also validated our results using a different fluorescent membrane probe, Nile Red (NR). The plasma membrane in the cells expressing expanded polyQ shows a shift toward increased membrane fluidity revealed by both LAURDAN and NR spectral phasors. This finding brings a new perspective in the understanding of the early stages of HD that can be used as a target for drug screening.One of the common characteristic of neurodegenerative diseases is the aggregation of specific proteins that leads to deposits in tissue or subcellular compartments. This is commonly known as protein misfolding or conformational disorder in Alzheimer's disease (AD), Parkinson's disease (PD), Huntington disease (HD) and other neurodegenerative disorders 1 . HD is a progressive genetic neurodegenerative disorder with complex pathogenies including protein aggregation and dysregulation of lipid homeostasis. The key event in such pathologies is the conversion of protein to an abnormal conformation that may lead to formation of toxic aggregates. In the case of HD, polyglutamine (PolyQ) aggregation is the hallmark of the disease. In the last decades, there has been an intense research effort to determine the toxicity of the aggregate species as protein aggregation progresses from monomeric to oligomeric and finally a mature inclusion 2,3 . This understanding is relevant since there are currently no effective measures or treatments of HD. Recent research shows that metabolism is also affected as a results of HD and indicates disturbed OXPHOS pathway and a shift of the metabolism toward more free NADH as the disease progresses that implies disruption of glucose uptake in HD cells compared to normal 4 . Besides glucose, lipid metabolism is also shown to be affected in HD and other neurodegenerative disorders [5][6][7][8] . Lipid and cholesterol are important cell plasma membrane components as they control normal cell function. In Alzheimer disease (AD), impaired lipid homeostasis is one of the early event in the disease 9 . The alteration in lipid composition can lead to instability in membrane and synaptic loss in AD 8 . Furthermore, rising evidence...

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Differential Dynamic and Structural Behavior of Lipid-Cholesterol Domains in Model Membranes

Cited by 46 publications

References 43 publications

Effect of Hydration and Packing Order on Large Unilamellar Vesicle Fusion: The Role of Cholesterol

Effect of Hydration and Packing Order on Large Unilamellar Vesicle Fusion: The Role of Cholesterol

Differential Effect of Plant Lipids on Membrane Organization

Alteration in Fluidity of Cell Plasma Membrane in Huntington Disease Revealed by Spectral Phasor Analysis

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