Sphingomyelin Acyl Chains Influence the Formation of Sphingomyelin- and Cholesterol-Enriched Domains

Engberg, Oskar; Lin, Kai‐Lan; Hautala, Victor; Slotte, J. Peter; Nyholm, Thomas K.M.

doi:10.1016/j.bpj.2020.11.001

Cited by 6 publications

(9 citation statements)

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“…59,69 Several recent studies have shown that small changes in a lipid's chemistry can alter its affinity for Chol, and thus change the size and stability of lateral heterogeneities. 52,56,[70][71][72][73][74] Here we see that KChol, an oxidation product of Chol, has significantly less affinity for DPPC over DOPC than Chol -and the result is a disruption of the macroscopic phase separation.…”

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confidence: 62%

Cholesterol Oxidation Modulates the Formation of Liquid-Ordered Domains in Model Membranes

Smith

Petrov

Lorenz

2021

Preprint

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7-ketocholesterol (KChol) is one of the most cytotoxic oxysterols found in the plasma membrane, and increased levels of KChol are associated with numerous pathologies. It is thought to induce apoptosis via inactivation of the phosphatidylinositol 3-kinase/Akt signaling pathway - a pathway that depends on lipid-rafts as signaling platforms. By means of coarse-grained molecular dynamics simulations, we demonstrate that KChol disrupts the liquid-liquid phase separation seen in an equimolar mixture of (dipalmitoylphosphatidylcholine) DPPC, (dioleoylphosphatidylcholine) DOPC, and Cholesterol (Chol). This disruption occurs via two mechanisms: i) KChol adopts a wider range of orientations with the membrane, which disrupts the packing of neighboring lipids and ii) KChol has no preference for DPPC over DOPC, which is the main driving force for lateral demixing in DPPC/DOPC/Chol membranes. This provides a molecular description of the means by which KChol induces apoptosis, and illustrates that a single chemical substitution to cholesterol can have a profound impact on the lateral organization of lipid membranes.

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confidence: 62%

Cholesterol Oxidation Modulates the Formation of Liquid-Ordered Domains in Model Membranes

Smith

Petrov

Lorenz

2021

Preprint

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“…Specific membrane lipids, for example sphingolipids, are important in the formation of ordered membrane lipid mosaic domains or ‘lipid rafts’ [ 38 , 43 , 44 , 45 , 46 , 47 ]. With phosphatidylcholine, sphingomyelins constitute more than one-half of the cell membrane phospholipids and are the most important companions of cholesterol in lipid domains or lipid rafts [ 47 , 48 ]. Small, ordered membrane rafts/domains assemble by preferential associations of cholesterol and saturated lipids.…”

Section: Some Important Interactions Of Proteins and Lipids In Biomem...mentioning

confidence: 99%

“…Small, ordered membrane rafts/domains assemble by preferential associations of cholesterol and saturated lipids. These rafts/domains are generally surrounded by liquid-phase lipids, and thus they are able to undergo membrane lateral movements [ 46 , 47 ]. Lipid rafts/domains can also selectively recruit additional lipids and proteins into their structures [ 30 , 43 , 44 , 45 , 46 , 47 ].…”

Section: Some Important Interactions Of Proteins and Lipids In Biomem...mentioning

confidence: 99%

“…These rafts/domains are generally surrounded by liquid-phase lipids, and thus they are able to undergo membrane lateral movements [ 46 , 47 ]. Lipid rafts/domains can also selectively recruit additional lipids and proteins into their structures [ 30 , 43 , 44 , 45 , 46 , 47 ]. Not all of the lipids within such mosaic domains are completely immobilized—they are still rotationally and laterally mobile to some degree and capable of slowly exchanging their lipids with bulk membrane lipids as well as with lipids in other membrane domains [ 30 , 46 , 47 ].…”

Section: Some Important Interactions Of Proteins and Lipids In Biomem...mentioning

confidence: 99%

“…Lipid rafts/domains can also selectively recruit additional lipids and proteins into their structures [ 30 , 43 , 44 , 45 , 46 , 47 ]. Not all of the lipids within such mosaic domains are completely immobilized—they are still rotationally and laterally mobile to some degree and capable of slowly exchanging their lipids with bulk membrane lipids as well as with lipids in other membrane domains [ 30 , 46 , 47 ]. The overall sizes of lipid domains, such as lipid rafts, are usually less than 300 nm in diameter; most are within 10–200 nm in diameter, with some slightly larger [ 49 , 50 , 51 ].…”

Section: Some Important Interactions Of Proteins and Lipids In Biomem...mentioning

confidence: 99%

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Fifty Years of the Fluid–Mosaic Model of Biomembrane Structure and Organization and Its Importance in Biomedicine with Particular Emphasis on Membrane Lipid Replacement

Nicolson

Ferreira

2022

Biomedicines

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The Fluid–Mosaic Model has been the accepted general or basic model for biomembrane structure and organization for the last 50 years. In order to establish a basic model for biomembranes, some general principles had to be established, such as thermodynamic assumptions, various molecular interactions, component dynamics, macromolecular organization and other features. Previous researchers placed most membrane proteins on the exterior and interior surfaces of lipid bilayers to form trimolecular structures or as lipoprotein units arranged as modular sheets. Such membrane models were structurally and thermodynamically unsound and did not allow independent lipid and protein lateral movements. The Fluid–Mosaic Membrane Model was the only model that accounted for these and other characteristics, such as membrane asymmetry, variable lateral movements of membrane components, cis- and transmembrane linkages and dynamic associations of membrane components into multimolecular complexes. The original version of the Fluid–Mosaic Membrane Model was never proposed as the ultimate molecular description of all biomembranes, but it did provide a basic framework for nanometer-scale biomembrane organization and dynamics. Because this model was based on available 1960s-era data, it could not explain all of the properties of various biomembranes discovered in subsequent years. However, the fundamental organizational and dynamic aspects of this model remain relevant to this day. After the first generation of this model was published, additional data on various structures associated with membranes were included, resulting in the addition of membrane-associated cytoskeletal, extracellular matrix and other structures, specialized lipid–lipid and lipid–protein domains, and other configurations that can affect membrane dynamics. The presence of such specialized membrane domains has significantly reduced the extent of the fluid lipid membrane matrix as first proposed, and biomembranes are now considered to be less fluid and more mosaic with some fluid areas, rather than a fluid matrix with predominantly mobile components. However, the fluid–lipid matrix regions remain very important in biomembranes, especially those involved in the binding and release of membrane lipid vesicles and the uptake of various nutrients. Membrane phospholipids can associate spontaneously to form lipid structures and vesicles that can fuse with various cellular membranes to transport lipids and other nutrients into cells and organelles and expel damaged lipids and toxic hydrophobic molecules from cells and tissues. This process and the clinical use of membrane phospholipid supplements has important implications for chronic illnesses and the support of healthy mitochondria, plasma membranes and other cellular membrane structures.

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Serotonergic drugs modulate the phase behavior of complex lipid bilayers

et al. 2022

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Sphingomyelin Acyl Chains Influence the Formation of Sphingomyelin- and Cholesterol-Enriched Domains

Cited by 6 publications

References 57 publications

Cholesterol Oxidation Modulates the Formation of Liquid-Ordered Domains in Model Membranes

Cholesterol Oxidation Modulates the Formation of Liquid-Ordered Domains in Model Membranes

Fifty Years of the Fluid–Mosaic Model of Biomembrane Structure and Organization and Its Importance in Biomedicine with Particular Emphasis on Membrane Lipid Replacement

Serotonergic drugs modulate the phase behavior of complex lipid bilayers

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