Formation of the liquid-ordered phase in fully hydrated mixtures of cholesterol and lysopalmitoylphosphatidylcholine

Gater, Deborah L.; Seddon, John M.; Law, Robert V.

doi:10.1039/b710726a

Cited by 12 publications

(18 citation statements)

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“…The cholesterol crystals are characterized by peaks centered at 34 and 17 Å (SAXS) and multiple sharp peaks in the wide angle region (WAXS Figure 7b inset). These are in good agreement with previous literature reports characterizing cholesterol crystal structure in isolation and lipid systems 52,59…”

Section: Resultssupporting

confidence: 93%

A Robust Liposomal Platform for Direct Colorimetric Detection of Sphingomyelinase Enzyme and Inhibitors

et al. 2018

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The enzyme sphingomyelinase (SMase) is an important biomarker for several diseases such as Niemann Pick’s, atherosclerosis, multiple sclerosis, and HIV. We present a two-component colorimetric SMase activity assay that is more sensitive and much faster than currently available commercial assays. Herein, SMase-triggered release of cysteine from a sphingomyelin (SM)-based liposome formulation with 60 mol % cholesterol causes gold nanoparticle (AuNP) aggregation, enabling colorimetric detection of SMase activities as low as 0.02 mU/mL, corresponding to 1.4 pM concentration. While the lipid composition offers a stable, nonleaky liposome platform with minimal background signal, high specificity toward SMase avoids cross-reactivity of other similar phospholipases. Notably, use of an SM-based liposome formulation accurately mimics the natural in vivo substrate: the cell membrane. We studied the physical rearrangement process of the lipid membrane during SMase-mediated hydrolysis of SM to ceramide using small- and wide-angle X-ray scattering. A change in lipid phase from a liquid to gel state bilayer with increasing concentration of ceramide accounts for the observed increase in membrane permeability and consequent release of encapsulated cysteine. We further demonstrated the effectiveness of the sensor in colorimetric screening of small-molecule drug candidates, paving the way for the identification of novel SMase inhibitors in minutes. Taken together, the simplicity, speed, sensitivity, and naked-eye readout of this assay offer huge potential in point-of-care diagnostics and high-throughput drug screening.

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Section: Resultssupporting

confidence: 93%

A Robust Liposomal Platform for Direct Colorimetric Detection of Sphingomyelinase Enzyme and Inhibitors

et al. 2018

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“…20 The acid-triggered degradation of charged non-phospholipid nanocarriers are relatively rare in literature, and have recently been implemented with fatty analogues of amines 21 and acids. 22 Here we report tetrahydropyrimidinone-based amphiphile ALA-11 that is quantitatively prepared in one step (Fig.…”

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confidence: 99%

“…These data show that the pH-responsiveness of the ALA-11 nanocarrier system can be modulated by cholesterol content for the short-term, pH-responsive release of hydrophobic compounds. 20,21 …”

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confidence: 99%

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Acid-responsive nanospheres from an asparagine-derived amphiphile

et al. 2015

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“…Under these experimental conditions, LPC forms a micellar solution. In comparison, LPC mixed in a 1:1 M ratio with cholesterol is likely in a lamellar phase, with the sample comprising a turbid suspension of multi-lamellar vesicles [ 29 , 30 ]. The turbidity of the ergosterol and CHS samples indicates that these mixtures were also not comprised of mixed micelles, and no evidence of micelles was found in dynamic light scattering (DLS) experiments, with all of these samples apparently consisting of larger aggregates (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Quantification of sterol-specific response in human macrophages using automated imaged-based analysis

et al. 2017

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BackgroundThe transformation of normal macrophage cells into lipid-laden foam cells is an important step in the progression of atherosclerosis. One major contributor to foam cell formation in vivo is the intracellular accumulation of cholesterol.MethodsHere, we report the effects of various combinations of low-density lipoprotein, sterols, lipids and other factors on human macrophages, using an automated image analysis program to quantitatively compare single cell properties, such as cell size and lipid content, in different conditions.ResultsWe observed that the addition of cholesterol caused an increase in average cell lipid content across a range of conditions. All of the sterol-lipid mixtures examined were capable of inducing increases in average cell lipid content, with variations in the distribution of the response, in cytotoxicity and in how the sterol-lipid combination interacted with other activating factors. For example, cholesterol and lipopolysaccharide acted synergistically to increase cell lipid content while also increasing cell survival compared with the addition of lipopolysaccharide alone. Additionally, ergosterol and cholesteryl hemisuccinate caused similar increases in lipid content but also exhibited considerably greater cytotoxicity than cholesterol.ConclusionsThe use of automated image analysis enables us to assess not only changes in average cell size and content, but also to rapidly and automatically compare population distributions based on simple fluorescence images. Our observations add to increasing understanding of the complex and multifactorial nature of foam-cell formation and provide a novel approach to assessing the heterogeneity of macrophage response to a variety of factors.Electronic supplementary materialThe online version of this article (10.1186/s12944-017-0629-9) contains supplementary material, which is available to authorized users.

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Formation of the liquid-ordered phase in fully hydrated mixtures of cholesterol and lysopalmitoylphosphatidylcholine

Cited by 12 publications

References 50 publications

A Robust Liposomal Platform for Direct Colorimetric Detection of Sphingomyelinase Enzyme and Inhibitors

A Robust Liposomal Platform for Direct Colorimetric Detection of Sphingomyelinase Enzyme and Inhibitors

Acid-responsive nanospheres from an asparagine-derived amphiphile

Quantification of sterol-specific response in human macrophages using automated imaged-based analysis

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