Sphingomyelins and ent-Sphingomyelins Form Homophilic Nano-Subdomains within Liquid Ordered Domains

Yano, Yo; Hanashima, Shinya; Tsuchikawa, Hiroshi; Yasuda, Tomokazu; Slotte, J. Peter; London, Erwin; Murata, Michio

doi:10.1016/j.bpj.2020.06.028

Cited by 17 publications

(4 citation statements)

References 55 publications

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“…When the F / F 0 ratios of POPC and PSM/Cho (1:1) were assumed to be the quenching rates in the disordered and ordered states, the L o /L d area ratio of POPC/PSM/Cho (1:1:1) was estimated to be 78:22. This ratio was comparable with the theoretical ratio of 76:24 obtained from the phase diagram of the POPC/PSM/Cho (1:1:1) membrane taking into account the reported area per lipid. − The TEMPO quenching conditions optimized for the model membrane were applied to examine the ratio of the ordered areas on the exosome membranes. The F / F 0 ratios of both milk and PC3 exosomes were approximately 60%.…”

Section: Resultssupporting

confidence: 71%

Fluorescence Spectroscopic Analysis of Lateral and Transbilayer Fluidity of Exosome Membranes

et al. 2022

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Exosomes are small extracellular vesicles (sEVs) involved in distal cell–cell communication and cancer migration by transferring functional cargo molecules. Membrane domains similar to lipid rafts are assumed to occur in exosome membranes and are involved in interactions with target cells. However, the bilayer membrane properties of these small vesicles have not been fully investigated. Therefore, we examined the fluidity, lateral domain separation, and transbilayer asymmetry of exosome membranes using fluorescence spectroscopy. Although there were some differences between the exosomes, TMA-DPH anisotropy showing moderate lipid chain order indicated that ordered phases comprised a significant proportion of exosome membranes. Selective TEMPO quenching of the TMA-DPH fluorescence in the liquid-disordered phase indicated that 40–50% of the exosome membrane area belonged to the ordered phase based on a phase-separated model. Furthermore, NBD-PC in the outer leaflet showed longer fluorescence lifetimes than those in the inner leaflets. Therefore, the exosome membranes maintained transbilayer asymmetry with a topology similar to that of the plasma membranes. In addition, the lateral and transbilayer orders of exosome membranes obtained from different cell lines varied, probably depending on the different membrane lipid components and compositions partially derived from donor cells. As these higher membrane orders and asymmetric topologies are similar to those of cell membranes with lipid rafts, raft-like functional domains are possibly enriched on exosome membranes. These domains likely play key roles in the biological functions and cellular uptake of exosomes by facilitating selective membrane interactions with target organs.

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Section: Resultssupporting

confidence: 71%

Fluorescence Spectroscopic Analysis of Lateral and Transbilayer Fluidity of Exosome Membranes

et al. 2022

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“…The liquid ordered state is characterized by a high level of order but relatively fast lateral diffusion. Recent studies indicate that the liquid ordered state is composed of gel/solid-like phospholipid or sphingolipid subdomains laterally separated by sterol-rich layers [32,33]. An analogy to the liquid ordered state would be a cluster of small icebergs separated by a thin layer of liquid so that they can laterally diffuse rapidly within the cluster relative to each other despite having a solid internal state.…”

Section: Membrane Physical State and Domain Formationmentioning

confidence: 99%

Ordered Domain (Raft) Formation in Asymmetric Vesicles and Its Induction upon Loss of Lipid Asymmetry in Artificial and Natural Membranes

London

2022

Membranes

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Lipid asymmetry, the difference in the lipid composition in the inner and outer lipid monolayers (leaflets) of a membrane, is an important feature of eukaryotic plasma membranes. Investigation of the biophysical consequences of lipid asymmetry has been aided by advances in the ability to prepare artificial asymmetric membranes, especially by use of cyclodextrin-catalyzed lipid exchange. This review summarizes recent studies with artificial asymmetric membranes which have identified conditions in which asymmetry can induce or suppress the ability of membranes to form ordered domains (rafts). A consequence of the latter effect is that, under some conditions, a loss of asymmetry can induce ordered domain formation. An analogous study in plasma membrane vesicles has demonstrated that asymmetry can also suppress domain formation in natural membranes. Thus, it is possible that a loss of asymmetry can induce domain formation in vivo.

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“…The sizes of the observed ND were in the range of 5-60 nm. In particular, Yano et al [34] examined the details of their formation by stearoyl-SMs (SSMs) using FRET measurements in lipid bilayers containing SSM and its enantiomer (ent-SSM), dioleoyl-phosphatidylcholine (DOPC), and Chol. In contrast to the uniform domains seen by microscopy, FRET analysis using fluorescent donor-and acceptor-labeled SSM showed distinct differences in SM and ent-SM colocalization within nanoscale distances.…”

Section: Model Lipid Membranesmentioning

confidence: 99%

“…Often, a kind of "stimulator" of the formation of NDs is Chol. In particular, Yano et al showed [34] that in mixtures with SM, Chol enhances the formation of H-bonds between SM molecules, limiting the conformational mobility of their acyl chains in the nonpolar region of the bilayer [70,71]. In turn, this contributes to the formation of NDs inside the L o phase of the membrane.…”

Section: Role Of H-bonds In Formation Of Ndsmentioning

confidence: 99%

Dynamic “Molecular Portraits” of Biomembranes Drawn by Their Lateral Nanoscale Inhomogeneities

Efremov

2021

IJMS

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To date, it has been reliably shown that the lipid bilayer/water interface can be thoroughly characterized by a sophisticated so-called “dynamic molecular portrait”. The latter reflects a combination of time-dependent surface distributions of various physicochemical properties, inherent in both model lipid bilayers and natural multi-component cell membranes. One of the most important features of biomembranes is their mosaicity, which is expressed in the constant presence of lateral inhomogeneities, the sizes and lifetimes of which vary in a wide range—from 1 to 103 nm and from 0.1 ns to milliseconds. In addition to the relatively well-studied macroscopic domains (so-called “rafts”), the analysis of micro- and nanoclusters (or domains) that form an instantaneous picture of the distribution of structural, dynamic, hydrophobic, electrical, etc., properties at the membrane-water interface is attracting increasing interest. This is because such nanodomains (NDs) have been proven to be crucial for the proper membrane functioning in cells. Therefore, an understanding with atomistic details the phenomena associated with NDs is required. The present mini-review describes the recent results of experimental and in silico studies of spontaneously formed NDs in lipid membranes. The main attention is paid to the methods of ND detection, characterization of their spatiotemporal parameters, the elucidation of the molecular mechanisms of their formation. Biological role of NDs in cell membranes is briefly discussed. Understanding such effects creates the basis for rational design of new prospective drugs, therapeutic approaches, and artificial membrane materials with specified properties.

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Sphingomyelins and ent-Sphingomyelins Form Homophilic Nano-Subdomains within Liquid Ordered Domains

Cited by 17 publications

References 55 publications

Fluorescence Spectroscopic Analysis of Lateral and Transbilayer Fluidity of Exosome Membranes

Fluorescence Spectroscopic Analysis of Lateral and Transbilayer Fluidity of Exosome Membranes

Ordered Domain (Raft) Formation in Asymmetric Vesicles and Its Induction upon Loss of Lipid Asymmetry in Artificial and Natural Membranes

Dynamic “Molecular Portraits” of Biomembranes Drawn by Their Lateral Nanoscale Inhomogeneities

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