Cholesterol Depletion from a Ceramide/Cholesterol Mixed Monolayer: A Brewster Angle Microscope Study

Mandal, Pritam; Noutsi, Pakiza; Chaı̈eb, Sahraoui

doi:10.1038/srep26907

Cited by 9 publications

(12 citation statements)

References 54 publications

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“…Cyclodextrins are cyclic oligosaccharides that, for many years, have been used to modulate the composition of cholesterol and other lipids in biological membranes and have also been used as pharmaceutical excipients in the formulation of hydrophobic drugs [ 1 , 2 ]. More recently, 2-Hydroxypropyl-β-cyclodextrins (HPβCDs) have gained attention as a potential therapeutic intervention for Niemann-Pick Disease Type C1 (NPC1), an autosomal-recessive, rare, fatally progressive, neurodegenerative lysosomal storage disease characterized by endo-lysosomal accumulation of cholesterol and other lipids [ 3 – 7 ].…”

Section: Introductionmentioning

confidence: 99%

Characterization of hydroxypropyl-beta-cyclodextrins used in the treatment of Niemann-Pick Disease type C1

et al. 2017

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2-Hydroxypropyl-beta-cyclodextrin (HPβCD) has gained recent attention as a potential therapeutic intervention in the treatment of the rare autosomal-recessive, neurodegenerative lysosomal storage disorder Niemann-Pick Disease Type C1 (NPC1). Notably, HPβCD formulations are not comprised of a single molecular species, but instead are complex mixtures of species with differing degrees of hydroxypropylation of the cyclodextrin ring. The degree of substitution is a critical aspect of the complex mixture as it influences binding to other molecules and thus could potentially modulate biological effects. VTS-270 (Kleptose HPB) and Trappsol® Cyclo™ are HPβCD products under investigation as novel treatments for NPC1. The purpose of the present work is to compare these two different products; analyses were based on ion distribution and abundance profiles using mass spectrometry methodology as a means for assessing key molecular distinctions between products. The method incorporated electrospray ionization and analysis with a linear low-field ion mobility quadrupole time-of-flight instrument. We observed that the number of hydroxypropyl groups (the degrees of substitution) are substantially different between the two products and greater in Trappsol Cyclo than in VTS-270. The principal ions of both samples are ammonium adducts. Isotope clusters for each of the major ions show doubly charged homodimers of the ammonium adducts. In addition, both products show doubly charged homodimers from adduction of both a proton and ammonium. Doubly charged heterodimers are also present, but are more intense in Trappsol Cyclo than in VTS-270. Based on the analytical differences observed between VTS-270 and Trappsol Cyclo with respect to the degree of substitution, the composition and fingerprint of the complex mixture, and the impurity profiles, these products cannot be considered to be the same; the potential biological and clinical implications of these differences are not presently known.

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Section: Introductionmentioning

confidence: 99%

Characterization of hydroxypropyl-beta-cyclodextrins used in the treatment of Niemann-Pick Disease type C1

et al. 2017

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“…MβCD-mediated cholesterol depletion efficiency can vary depending on the lipid composition. , For example, cholesterol is preferentially removed from nonlipid raft regions in phospholipid/cholesterol mixed vesicles. Cholesterol removal from lipid rafts is initiated at high concentrations of MβCD .…”

Section: Resultsmentioning

confidence: 99%

Probing Physical Properties of the Cellular Membrane in Senescent Cells by Fluorescence Imaging

Heo

Gwak

et al. 2021

J. Phys. Chem. B

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Cellular senescence is the irreversible cell cycle arrest in response to various types of stress. Although the plasma membrane and its composition are significantly affected by cellular senescence, detailed studies on the physical properties of the plasma membrane have shown inconclusive results. In this study, we utilized both ensemble and single-molecule fluorescence imaging to investigate how membrane properties, such as fluidity, hydrophobicity, and ganglioside GM1 level are affected by cellular senescence. The diffusion coefficient of lipid probes, as well as the type of diffusion determined by an exponent α, which is the slope of the log−log plot of mean squared displacement as a function of time lag, were analyzed. We found that the number of molecules with a lower diffusion coefficient increased as cells became senescent. The changes in the population with a lower diffusion coefficient, observed after methyl-β-cyclodextrin treatment, and the increase in ceramide levels, detected using a ceramide-specific antibody, suggest that ceramide-rich lipid rafts were enhanced in senescent cells. Our results emphasize the importance of membrane properties in cellular senescence and might serve as a base for in-depth studies to determine how such domains facilitate the signaling pathway specific to cellular senescence.

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“…This is important because as was stated above, the LS present a very complex organization at the interface and in the adjacent liquid phase [170], and the use of techniques such as Brewster angle microscopy (BAM), AFM, surface force apparatus (SFA), ellipsometry, infrared reflection absorption spectroscopy (IRRAS), or epifluorescence microscopy, and their combinations with tensiometric techniques (mainly Langmuir film balances) are very powerful tools for deepening knowledge on the impact of particles on the organization of LS films in the micrometric and submicrometric scale [171][172][173][174]. Furthermore, there are more sophisticated tools, including neutron reflectivity or synchrotron grazing angle X-ray diffractions which may also be useful in the evaluation of the impact of particulate matter on LS interfacial organization [108,134,[175][176][177][178][179][180][181][182].…”

Section: Experimental Toolsmentioning

confidence: 99%

Fluid Films as Models for Understanding the Impact of Inhaled Particles in Lung Surfactant Layers

Guzmán

2022

Coatings

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Pollution is currently a public health problem associated with different cardiovascular and respiratory diseases. These are commonly originated as a result of the pollutant transport to the alveolar cavity after their inhalation. Once pollutants enter the alveolar cavity, they are deposited on the lung surfactant (LS) film, altering their mechanical performance which increases the respiratory work and can induce a premature alveolar collapse. Furthermore, the interactions of pollutants with LS can induce the formation of an LS corona decorating the pollutant surface, favoring their penetration into the bloodstream and distribution along different organs. Therefore, it is necessary to understand the most fundamental aspects of the interaction of particulate pollutants with LS to mitigate their effects, and design therapeutic strategies. However, the use of animal models is often invasive, and requires a careful examination of different bioethics aspects. This makes it necessary to design in vitro models mimicking some physico-chemical aspects with relevance for LS performance, which can be done by exploiting the tools provided by the science and technology of interfaces to shed light on the most fundamental physico-chemical bases governing the interaction between LS and particulate matter. This review provides an updated perspective of the use of fluid films of LS models for shedding light on the potential impact of particulate matter in the performance of LS film. It should be noted that even though the used model systems cannot account for some physiological aspects, it is expected that the information contained in this review can contribute on the understanding of the potential toxicological effects of air pollution.

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Cholesterol Depletion from a Ceramide/Cholesterol Mixed Monolayer: A Brewster Angle Microscope Study

Cited by 9 publications

References 54 publications

Characterization of hydroxypropyl-beta-cyclodextrins used in the treatment of Niemann-Pick Disease type C1

Characterization of hydroxypropyl-beta-cyclodextrins used in the treatment of Niemann-Pick Disease type C1

Probing Physical Properties of the Cellular Membrane in Senescent Cells by Fluorescence Imaging

Fluid Films as Models for Understanding the Impact of Inhaled Particles in Lung Surfactant Layers

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