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  1. Article ; Online: Need for more focus on lipid species in studies of biological and model membranes.

    Skotland, Tore / Sandvig, Kirsten

    Progress in lipid research

    2022  Volume 86, Page(s) 101160

    Abstract: The lipid composition of cellular membranes can impact a number of physiological processes such as signaling, cell migration, endocytosis and intracellular transport. In this article we focus on some aspects concerning analysis of lipids and research on ... ...

    Abstract The lipid composition of cellular membranes can impact a number of physiological processes such as signaling, cell migration, endocytosis and intracellular transport. In this article we focus on some aspects concerning analysis of lipids and research on lipid structure and function in mammalian cells that in our opinion have not obtained sufficient attention. This includes interleaflet coupling between the two layers of the membrane, and the role of lipid species, i.e. the role of the complete structure of the lipids, including lipid chain length and the position of double bonds. We highlight the role of PS species for membrane function. We also discuss the large diversity of PS species in different biological samples and the possible functional consequences, and we provide an overview of PS species from 40 different samples. Furthermore, recent studies show that there seems to be a coregulation concerning the levels of sphingolipids and ether lipids. We review and discuss the published data indicating such a coregulation. Moreover, we point to some of the pitfalls in the field of lipidomics and present suggestions for improvement. Finally, we discuss the importance of using asymmetric membrane models with a composition of lipid species that are common in biological membranes.
    MeSH term(s) Animals ; Biological Transport ; Cell Membrane/metabolism ; Lipidomics ; Mammals/metabolism ; Sphingolipids/metabolism
    Chemical Substances Sphingolipids
    Language English
    Publishing date 2022-03-11
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 282560-0
    ISSN 1873-2194 ; 0079-6832 ; 0163-7827
    ISSN (online) 1873-2194
    ISSN 0079-6832 ; 0163-7827
    DOI 10.1016/j.plipres.2022.101160
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Lipids in Extracellular Vesicles: What Can Be Learned about Membrane Structure and Function?

    Skotland, Tore / Llorente, Alicia / Sandvig, Kirsten

    Cold Spring Harbor perspectives in biology

    2023  Volume 15, Issue 8

    Abstract: Extracellular vesicles, such as exosomes, can be used as interesting models to study the structure and function of biological membranes as these vesicles contain only one membrane (i.e., one lipid bilayer). In addition to lipids, they contain proteins, ... ...

    Abstract Extracellular vesicles, such as exosomes, can be used as interesting models to study the structure and function of biological membranes as these vesicles contain only one membrane (i.e., one lipid bilayer). In addition to lipids, they contain proteins, nucleic acids, and various other molecules. The lipid composition of exosomes is here compared to HIV particles and detergent-resistant membranes, which also have a high content of sphingolipids, cholesterol, and phosphatidylserine (PS). We discuss interactions between the lipids in the two bilayers, and especially those between PS 18:0/18:1 in the inner leaflet and the very-long-chain sphingolipids in the outer leaflet, and the importance of cholesterol for these interactions. We also briefly discuss the involvement of ether-linked phospholipids (PLs) in such lipid raft-like structures, and the possible involvement of these and other lipid classes in the formation of exosomes. The urgent need to improve the quality of quantitative lipidomic studies is highlighted.
    MeSH term(s) Lipid Bilayers/chemistry ; Lipid Bilayers/metabolism ; Cell Membrane/metabolism ; Sphingolipids/metabolism ; Extracellular Vesicles/metabolism ; Cholesterol
    Chemical Substances Lipid Bilayers ; Sphingolipids ; Cholesterol (97C5T2UQ7J)
    Language English
    Publishing date 2023-08-01
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ISSN 1943-0264
    ISSN (online) 1943-0264
    DOI 10.1101/cshperspect.a041415
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Biodistribution, pharmacokinetics and excretion studies of intravenously injected nanoparticles and extracellular vesicles: Possibilities and challenges.

    Skotland, Tore / Iversen, Tore Geir / Llorente, Alicia / Sandvig, Kirsten

    Advanced drug delivery reviews

    2022  Volume 186, Page(s) 114326

    Abstract: There is a large interest in developing nanoparticles and extracellular vesicles for delivery of therapeutics or imaging agents. Regulatory approval of such products requires knowledge about their biodistribution, metabolism and excretion. We here ... ...

    Abstract There is a large interest in developing nanoparticles and extracellular vesicles for delivery of therapeutics or imaging agents. Regulatory approval of such products requires knowledge about their biodistribution, metabolism and excretion. We here discuss possibilities and challenges of methods used for such studies, which most often are performed after labelling with radioactive isotopes or fluorescent molecules. It is important to evaluate if the labelled and unlabeled products can be expected to behave similarly in the body. Furthermore, one needs to critically consider whether the labels are still associated with the product at the time of analyses. We discuss advantages and disadvantages of different imaging modalities such as PET, SPECT, MRI, CT, ultrasound and optical imaging for whole-body biodistribution, and describe how to estimate the amount of labelled product in harvested organs and tissue. Microscopy of cells and tissues and various mass spectrometry methods are also discussed in this review.
    MeSH term(s) Extracellular Vesicles ; Humans ; Nanoparticles/chemistry ; Optical Imaging ; Tissue Distribution ; Tomography, Emission-Computed, Single-Photon
    Language English
    Publishing date 2022-05-16
    Publishing country Netherlands
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 639113-8
    ISSN 1872-8294 ; 0169-409X
    ISSN (online) 1872-8294
    ISSN 0169-409X
    DOI 10.1016/j.addr.2022.114326
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The Protein Toxins Ricin and Shiga Toxin as Tools to Explore Cellular Mechanisms of Internalization and Intracellular Transport.

    Sandvig, Kirsten / Kavaliauskiene, Simona / Skotland, Tore

    Toxins

    2021  Volume 13, Issue 6

    Abstract: Protein toxins secreted by bacteria and found in plants can be threats to human health. However, their extreme toxicity can also be exploited in different ways, e.g., to produce hybrid toxins directed against cancer cells and to study transport ... ...

    Abstract Protein toxins secreted by bacteria and found in plants can be threats to human health. However, their extreme toxicity can also be exploited in different ways, e.g., to produce hybrid toxins directed against cancer cells and to study transport mechanisms in cells. Investigations during the last decades have shown how powerful these molecules are as tools in cell biological research. Here, we first present a partly historical overview, with emphasis on Shiga toxin and ricin, of how such toxins have been used to characterize processes and proteins of importance for their trafficking. In the second half of the article, we describe how one can now use toxins to investigate the role of lipid classes for intracellular transport. In recent years, it has become possible to quantify hundreds of lipid species using mass spectrometry analysis. Thus, it is also now possible to explore the importance of lipid species in intracellular transport. The detailed analyses of changes in lipids seen under conditions of inhibited toxin transport reveal previously unknown connections between syntheses of lipid classes and demonstrate the ability of cells to compensate under given conditions.
    MeSH term(s) Animals ; Biological Transport ; Cell Count ; Endocytosis ; Endosomes/metabolism ; Golgi Apparatus/metabolism ; Humans ; Membrane Microdomains/metabolism ; Protein Transport ; Ricin/metabolism ; Shiga Toxin/metabolism ; Trihexosylceramides/analysis
    Chemical Substances Trihexosylceramides ; globotriaosylceramide (71965-57-6) ; Shiga Toxin (75757-64-1) ; Ricin (9009-86-3)
    Language English
    Publishing date 2021-05-25
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2518395-3
    ISSN 2072-6651 ; 2072-6651
    ISSN (online) 2072-6651
    ISSN 2072-6651
    DOI 10.3390/toxins13060377
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The role of PS 18:0/18:1 in membrane function.

    Skotland, Tore / Sandvig, Kirsten

    Nature communications

    2019  Volume 10, Issue 1, Page(s) 2752

    Abstract: Various studies have demonstrated that the two leaflets of cellular membranes interact, potentially through so-called interdigitation between the fatty acyl groups. While the molecular mechanism underlying interleaflet coupling remains to be fully ... ...

    Abstract Various studies have demonstrated that the two leaflets of cellular membranes interact, potentially through so-called interdigitation between the fatty acyl groups. While the molecular mechanism underlying interleaflet coupling remains to be fully understood, recent results suggest interactions between the very-long-chain sphingolipids in the outer leaflet, and phosphatidylserine PS18:0/18:1 in the inner leaflet, and an important role for cholesterol for these interactions. Here we review the evidence that cross-linking of sphingolipids may result in clustering of phosphatidylserine and transfer of signals to the cytosol. Although much remains to be uncovered, the molecular properties and abundance of PS 18:0/18:1 suggest a unique role for this lipid.
    MeSH term(s) Animals ; Cell Line ; Cell Membrane/physiology ; Cholesterol/metabolism ; Cross-Linking Reagents/metabolism ; Cytosol/physiology ; Humans ; Lipid Bilayers/metabolism ; Phosphatidylserines/metabolism ; Sphingolipids/metabolism
    Chemical Substances Cross-Linking Reagents ; Lipid Bilayers ; Phosphatidylserines ; Sphingolipids ; Cholesterol (97C5T2UQ7J)
    Language English
    Publishing date 2019-06-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-019-10711-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The role of PS 18:0/18:1 in membrane function

    Tore Skotland / Kirsten Sandvig

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 10

    Abstract: There are several lines of evidence for interactions between the two membrane leaflets in cells. In this review the authors discuss the transmembrane coupling of lipids, the involvement of phosphatidyl serine species PS 18:0/18:1, and their importance ... ...

    Abstract There are several lines of evidence for interactions between the two membrane leaflets in cells. In this review the authors discuss the transmembrane coupling of lipids, the involvement of phosphatidyl serine species PS 18:0/18:1, and their importance for various cellular processes.
    Keywords Science ; Q
    Language English
    Publishing date 2019-06-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: The role of PS 18:0/18:1 in membrane function

    Tore Skotland / Kirsten Sandvig

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 10

    Abstract: There are several lines of evidence for interactions between the two membrane leaflets in cells. In this review the authors discuss the transmembrane coupling of lipids, the involvement of phosphatidyl serine species PS 18:0/18:1, and their importance ... ...

    Abstract There are several lines of evidence for interactions between the two membrane leaflets in cells. In this review the authors discuss the transmembrane coupling of lipids, the involvement of phosphatidyl serine species PS 18:0/18:1, and their importance for various cellular processes.
    Keywords Science ; Q
    Language English
    Publishing date 2019-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Cellular uptake of nanoparticles

    Tore Skotland / Tore Geir Iversen / Kirsten Sandvig

    Precision Nanomedicine (2021)

    Involvement of caveolae?

    2021  

    Abstract: We here discuss shortly some pitfalls and challenges when investigating which endocytic mechanisms that are involved in cellular uptake of nanoparticles. We specifically discuss some common misunderstandings regarding studies claimed to demonstrate ... ...

    Abstract We here discuss shortly some pitfalls and challenges when investigating which endocytic mechanisms that are involved in cellular uptake of nanoparticles. We specifically discuss some common misunderstandings regarding studies claimed to demonstrate uptake via caveolae. Scientists in the nanomedicine field should be aware of that reduction in the membrane content of cholesterol by adding methyl-β-cyclodextrin not only removes caveolae, but inhibits other uptake mechanisms, such as macropinocytosis, as well. Furthermore, the general tyrosine kinase inhibitor genistein is not a specific inhibitor of uptake from caveolae. Moreover, one can still see that scientists in the field write that they want to direct transport of their particles to caveolae and caveosomes to avoid lysosomal degradation. However, caveosomes are artefacts caused by overexpression of caveolin-1 constructs, and ligands or particles taken up by caveolae are transported to endosomes and lysosomes as reported for other types of endocytosis.
    Keywords Medicine ; R ; Medical technology ; R855-855.5
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Andover House Inc.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: The Protein Toxins Ricin and Shiga Toxin as Tools to Explore Cellular Mechanisms of Internalization and Intracellular Transport

    Kirsten Sandvig / Simona Kavaliauskiene / Tore Skotland

    Toxins, Vol 13, Iss 377, p

    2021  Volume 377

    Abstract: Protein toxins secreted by bacteria and found in plants can be threats to human health. However, their extreme toxicity can also be exploited in different ways, e.g., to produce hybrid toxins directed against cancer cells and to study transport ... ...

    Abstract Protein toxins secreted by bacteria and found in plants can be threats to human health. However, their extreme toxicity can also be exploited in different ways, e.g., to produce hybrid toxins directed against cancer cells and to study transport mechanisms in cells. Investigations during the last decades have shown how powerful these molecules are as tools in cell biological research. Here, we first present a partly historical overview, with emphasis on Shiga toxin and ricin, of how such toxins have been used to characterize processes and proteins of importance for their trafficking. In the second half of the article, we describe how one can now use toxins to investigate the role of lipid classes for intracellular transport. In recent years, it has become possible to quantify hundreds of lipid species using mass spectrometry analysis. Thus, it is also now possible to explore the importance of lipid species in intracellular transport. The detailed analyses of changes in lipids seen under conditions of inhibited toxin transport reveal previously unknown connections between syntheses of lipid classes and demonstrate the ability of cells to compensate under given conditions.
    Keywords endocytosis ; intracellular transport ; Golgi apparatus ; endoplasmic reticulum ; membranes ; lipids ; Medicine ; R
    Subject code 612
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: An emerging focus on lipids in extracellular vesicles.

    Skotland, Tore / Sagini, Krizia / Sandvig, Kirsten / Llorente, Alicia

    Advanced drug delivery reviews

    2020  Volume 159, Page(s) 308–321

    Abstract: Extracellular vesicles contain a lipid bilayer membrane that protects the encapsulated material, such as proteins, nucleic acids, lipids and metabolites, from the extracellular environment. These vesicles are released from cells via different mechanisms. ...

    Abstract Extracellular vesicles contain a lipid bilayer membrane that protects the encapsulated material, such as proteins, nucleic acids, lipids and metabolites, from the extracellular environment. These vesicles are released from cells via different mechanisms. During recent years extracellular vesicles have been studied as possible biomarkers for different diseases, as biological nanoparticles for drug delivery, and in basic studies as a tool to understand the structure of biological membranes and the mechanisms involved in vesicular trafficking. Lipids are essential molecular components of extracellular vesicles, but at the moment our knowledge about the lipid composition and the function of lipids in these vesicles is limited. However, the interest of the research community in these molecules is increasing as their role in extracellular vesicles is starting to be acknowledged. In this review, we will present the status of the field and describe what is needed to bring it forward.
    MeSH term(s) Animals ; Extracellular Vesicles/metabolism ; Humans ; Lipid Metabolism ; Lipids
    Chemical Substances Lipids
    Language English
    Publishing date 2020-03-07
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 639113-8
    ISSN 1872-8294 ; 0169-409X
    ISSN (online) 1872-8294
    ISSN 0169-409X
    DOI 10.1016/j.addr.2020.03.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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