Journal articles on the topic 'Model lipid membrane'
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1
Nicolson, Garth L., and Gonzalo Ferreira de Mattos. "A Brief Introduction to Some Aspects of the Fluid–Mosaic Model of Cell Membrane Structure and Its Importance in Membrane Lipid Replacement." Membranes 11, no. 12 (November 29, 2021): 947. http://dx.doi.org/10.3390/membranes11120947.
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Early cell membrane models placed most proteins external to lipid bilayers in trimolecular structures or as modular lipoprotein units. These thermodynamically untenable structures did not allow lipid lateral movements independent of membrane proteins. The Fluid–Mosaic Membrane Model accounted for these and other properties, such as membrane asymmetry, variable lateral mobilities of membrane components and their associations with dynamic complexes. Integral membrane proteins can transform into globular structures that are intercalated to various degrees into a heterogeneous lipid bilayer matrix. This simplified version of cell membrane structure was never proposed as the ultimate biomembrane description, but it provided a basic nanometer scale framework for membrane organization. Subsequently, the structures associated with membranes were considered, including peripheral membrane proteins, and cytoskeletal and extracellular matrix components that restricted lateral mobility. In addition, lipid–lipid and lipid–protein membrane domains, essential for cellular signaling, were proposed and eventually discovered. The presence of specialized membrane domains significantly reduced the extent of the fluid lipid matrix, so membranes have become more mosaic with some fluid areas over time. However, the fluid regions of membranes are very important in lipid transport and exchange. Various lipid globules, droplets, vesicles and other membranes can fuse to incorporate new lipids or expel damaged lipids from membranes, or they can be internalized in endosomes that eventually fuse with other internal vesicles and membranes. They can also be externalized in a reverse process and released as extracellular vesicles and exosomes. In this Special Issue, the use of membrane phospholipids to modify cellular membranes in order to modulate clinically relevant host properties is considered.
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Nicolson, Garth L., and Gonzalo Ferreira de Mattos. "Fifty Years of the Fluid–Mosaic Model of Biomembrane Structure and Organization and Its Importance in Biomedicine with Particular Emphasis on Membrane Lipid Replacement." Biomedicines 10, no. 7 (July 15, 2022): 1711. http://dx.doi.org/10.3390/biomedicines10071711.
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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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Scott, Haden L., Kristen B. Kennison, Thais A. Enoki, Milka Doktorova, Jacob J. Kinnun, Frederick A. Heberle, and John Katsaras. "Model Membrane Systems Used to Study Plasma Membrane Lipid Asymmetry." Symmetry 13, no. 8 (July 26, 2021): 1356. http://dx.doi.org/10.3390/sym13081356.
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It is well known that the lipid distribution in the bilayer leaflets of mammalian plasma membranes (PMs) is not symmetric. Despite this, model membrane studies have largely relied on chemically symmetric model membranes for the study of lipid–lipid and lipid–protein interactions. This is primarily due to the difficulty in preparing stable, asymmetric model membranes that are amenable to biophysical studies. However, in the last 20 years, efforts have been made in producing more biologically faithful model membranes. Here, we review several recently developed experimental and computational techniques for the robust generation of asymmetric model membranes and highlight a new and particularly promising technique to study membrane asymmetry.
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Wang, Anna, and Jack W. Szostak. "Lipid constituents of model protocell membranes." Emerging Topics in Life Sciences 3, no. 5 (July 15, 2019): 537–42. http://dx.doi.org/10.1042/etls20190021.
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Primitive life must have possessed the essential features of modern cellular life, but without highly evolved proteins to perform dynamic functions such as nutrient transport and membrane remodeling. Here, we consider the membrane properties of protocells — minimal cells with hereditary material, capable of growth and division — and how these properties place restrictions on the components of the membrane. For example, the lipids of modern membranes are diacyl amphiphilic molecules containing well-over 20 carbons in total. Without proteins, these membranes are very stable and kinetically trapped. This inertness, combined with the need for enzymes to synthesize them, makes modern diacyl amphiphiles unsuitable candidates for the earliest membranes on Earth. We, therefore, discuss the progress made thus far with single-chained amphiphiles, including fatty acids and mixtures of fatty acids with related molecules, and the membrane-related research that must be undertaken to gain more insight into the origins of cellular life.
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Duda, Mariusz, Katarzyna Kawula, Anna Pawlak, Tadeusz Sarna, and Anna Wisniewska-Becker. "EPR Studies on the Properties of Model Photoreceptor Membranes Made of Natural and Synthetic Lipids." Cell Biochemistry and Biophysics 75, no. 3-4 (April 17, 2017): 433–42. http://dx.doi.org/10.1007/s12013-017-0795-4.
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Abstract The membranes of retina photoreceptors have unique lipid composition. They contain a high concentration of polyunsaturated docosahexaenoic acid, with six double bonds, and are enriched in phosphatidylethanolamines. Based on their phospholipid composition and cholesterol content, membranes of photoreceptors can be divided into three types: plasma membrane, young disks membranes, and old disks membranes. High amount of docosahexaenoic acid, abundant illumination, and high respiratory demands make these membranes sensitive to oxidative stress and lipid peroxidation. Human retinas are not easily available for research, therefore most research is done on bovine retinas. However, to follow, in a controlled manner, the changes in membrane properties caused by different factors it seems advisable to apply carefully prepared models of photoreceptor membranes. Using synthetic lipids we prepared liposome models of three types of photoreceptor membranes, and by means of electron paramagnetic resonance spectroscopy and spin labeling technique we compared polarity and fluidity of those model membranes with the properties of membranes consisting of natural lipids extracted from photoreceptor outer segments of bovine retinas. Additionally, we studied the effect of oxidation on the membrane properties in the presence and in the absence of zeaxanthin, which is an antioxidant naturally present in the human retina. The results show that there are significant differences in polarity and fluidity between all investigated membranes, which reflect differences in their lipid composition. The properties of the membranes made of natural photoreceptor outer segment lipids are most similar to the ones of the models of old disks membranes. Oxidation did not change the membrane properties significantly; however, a slight ordering effect was observed in liposomes made of natural photoreceptor outer segment lipids and in the model of old disks membranes. Zeaxanthin affected polarity and fluidity mostly in the model of old disks membranes. The results show that by careful selection and appropriate proportions of lipid mixtures, it is possible to obtain synthetic membranes of the properties similar to the natural ones.
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Naumowicz, Monika. "Electrical Properties of Model Lipid Membranes." Membranes 12, no. 2 (February 21, 2022): 248. http://dx.doi.org/10.3390/membranes12020248.
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Biological membranes are essential components of the living systems, and processes occurring with their participation are related mainly to electric phenomena such as signal transduction, existence of membrane potentials, and transport through the membrane [...]
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Waring, Alan J., Sylvia S. L. Harwig, and Robert L. Lehrer. "Structure and Activity of Protegiun-1 in Model Lipid Membranes." Protein & Peptide Letters 3, no. 3 (June 1996): 177–84. http://dx.doi.org/10.2174/092986650303220615100109.
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Protegrin (PG)-1, an antimicrobial peptide from porcine leukocytes, mediated the release of encapsulated fluorescent dye from vesicles of simulated microbial lipids, suggesting that the peptide interacted strongly with membrane-mimetic ensembles. Circular dichroism measurements of PG-1 in membrane-lipid dispersions and liposomal systems indicated that the peptide assumed a predominantly β-sheet conformation in these environments. Fourier transform infrared measurements of the peptide in microbial lipid films showed that the P sheet component was oriented approximately parallel to the surface of the lipid film The ability of PG-1 to associate with and lyse model microbial-lipid membranes is likely to underlie its potent antibiotic properties.
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Kure, Jakob L., Camilla B. Andersen, Thomas E. Rasmussen, B. Christoffer Lagerholm, and Eva C. Arnspang. "Defining the Diffusion in Model Membranes Using Line Fluorescence Recovery after Photobleaching." Membranes 10, no. 12 (December 17, 2020): 434. http://dx.doi.org/10.3390/membranes10120434.
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In this study, we explore the use of line FRAP to detect diffusion in synthetic lipid membranes. The study of the dynamics of these membrane lipids can, however, be challenging. The diffusion in two different synthetic membranes consisting of the lipid mixtures 1:1 DOPC:DPPC and 2:2:1 DOPC:DPPC:Cholesterol was studied with line FRAP. A correlation between diffusion coefficient and temperature was found to be dependent on the morphology of the membrane. We suggest line FRAP as a promising accessible and simple technique to study diffusion in plasma membranes.
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Kahya, Nicoletta. "Light on fluorescent lipids in rafts: a lesson from model membranes." Biochemical Journal 430, no. 3 (August 27, 2010): e7-e9. http://dx.doi.org/10.1042/bj20101196.
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Tracking fluorescent lipids in cellular membranes has been applied for decades to shed light on membrane trafficking, sorting, endocytosis and exocytosis, viral entry, and to understand the functional relevance of membrane heterogeneity, phase separation and lipid rafts. However, fluorescent probes may display different organizing behaviour from their corresponding endogenous lipids. A full characterization of these probes is therefore required for proper interpretation of fluorescence microscopy data in complex membrane systems. Model membrane studies provide essential clues that guide us to design and interpret our experiments, help us to avoid pitfalls and resolve artefacts in complex cellular environments. In the present issue of the Biochemical Journal, Juhasz, Davis and Sharom demonstrate the importance of testing lipid probes systematically in heterogeneous model membranes of specific composition and well-defined thermodynamic properties. The phase-partitioning behaviour of fluorescent probes, alone and/or in combination, cannot simply be assumed, but has to be fully characterized.
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Walczewska, Anna, Barbara Dziedzic, Dawid Stulczewski, and Emilia Zgórzyńska. "Cell membranes. Molecular lipid therapy." Postępy Higieny i Medycyny Doświadczalnej 71 (December 31, 2017): 1239–50. http://dx.doi.org/10.5604/01.3001.0010.7749.
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Membrane lipids, due to diverse molecular structures, electric charge and different functional characteristic, have a profound role in multiple cytophysiological processes. A better understanding of the membrane structure and changes of its function in a wide range of diseases gave rise to a new approach termed membrane lipid therapy and directed to modifying the membranes. The strategies directed to membrane involve a direct regulation of membrane lipid composition that causes a change of the transmembrane protein function and modifies the organization of membrane microdomains, or regulation of enzyme activity and gene expression to alter membrane lipid composition. Membrane therapy assumes the use of new molecules specifically designed to modify lipid composition and function of abnormal signaling proteins. Therefore, modifications of the lipid composition and organization of membrane microdomains become pharmacological targets to reverse pathological changes in the profile of enzymatically and non-enzymatically generated lipid derivatives or to modify signaling pathways in the cell. The present monography is an update of the canonical membrane model by Singer-Nicolson and describes the therapeutic targets related to the regulation of the composition and organization of the lipids in the plasma membrane.
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García-Arribas, Aritz B., Félix M. Goñi, and Alicia Alonso. "Lipid Self-Assemblies under the Atomic Force Microscope." International Journal of Molecular Sciences 22, no. 18 (September 18, 2021): 10085. http://dx.doi.org/10.3390/ijms221810085.
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Lipid model membranes are important tools in the study of biophysical processes such as lipid self-assembly and lipid–lipid interactions in cell membranes. The use of model systems to adequate and modulate complexity helps in the understanding of many events that occur in cellular membranes, that exhibit a wide variety of components, including lipids of different subfamilies (e.g., phospholipids, sphingolipids, sterols…), in addition to proteins and sugars. The capacity of lipids to segregate by themselves into different phases at the nanoscale (nanodomains) is an intriguing feature that is yet to be fully characterized in vivo due to the proposed transient nature of these domains in living systems. Model lipid membranes, instead, have the advantage of (usually) greater phase stability, together with the possibility of fully controlling the system lipid composition. Atomic force microscopy (AFM) is a powerful tool to detect the presence of meso- and nanodomains in a lipid membrane. It also allows the direct quantification of nanomechanical resistance in each phase present. In this review, we explore the main kinds of lipid assemblies used as model membranes and describe AFM experiments on model membranes. In addition, we discuss how these assemblies have extended our knowledge of membrane biophysics over the last two decades, particularly in issues related to the variability of different model membranes and the impact of supports/cytoskeleton on lipid behavior, such as segregated domain size or bilayer leaflet uncoupling.
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Braunagel, Julia, Ann Junghans, and Ingo Köper. "Membrane-Based Sensing Approaches." Australian Journal of Chemistry 64, no. 1 (2011): 54. http://dx.doi.org/10.1071/ch10347.
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Tethered bilayer lipid membranes can be used as model platforms to host membrane proteins or membrane-active peptides, which can act as transducers in sensing applications. Here we present the synthesis and characterization of a valinomycin derivative, a depsipeptide that has been functionalized to serve as a redox probe in a lipid bilayer. In addition, we discuss the influence of the molecular structure of the lipid bilayer on its ability to host proteins. By using electrical impedance techniques as well as neutron scattering experiments, a clear correlation between the packing density of the lipids forming the membrane and its ability to host membrane proteins could be shown.
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Janas, T., K. Nowotarski, W. I. Gruszecki, and T. Janas. "The effect of hexadecaprenol on molecular organisation and transport properties of model membranes." Acta Biochimica Polonica 47, no. 3 (September 30, 2000): 661–73. http://dx.doi.org/10.18388/abp.2000_3987.
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The Langmuir monolayer technique and voltammetric analysis were used to investigate the properties of model lipid membranes prepared from dioleoylphosphatidylcholine (DOPC), hexadecaprenol (C80), and their mixtures. Surface pressure-molecular area isotherms, current-voltage characteristics, and membrane conductance-temperature were measured. Molecular area isobars, specific molecular areas, excess free energy of mixing, collapse pressure and collapse area were determined for lipid monolayers. Membrane conductance, activation energy of ion migration across the membrane, and membrane permeability coefficient for chloride ions were determined for lipid bilayers. Hexadecaprenol decreases the activation energy and increases membrane conductance and membrane permeability coefficient. The results of monolayer and bilayer investigations show that some electrical, transport and packing properties of lipid membranes change under the influence of hexadecaprenol. The results indicate that hexadecaprenol modulates the molecular organisation of the membrane and that the specific molecular area of polyprenol molecules depends on the relative concentration of polyprenols in membranes. We suggest that hexadecaprenol modifies lipid membranes by the formation of fluid microdomains. The results also indicate that electrical transmembrane potential can accelerate the formation of pores in lipid bilayers modified by long chain polyprenols.
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Batenburg, A. M., and B. de Kruijff. "Modulation of membrane surface curvature by peptide-lipid interactions." Bioscience Reports 8, no. 4 (August 1, 1988): 299–307. http://dx.doi.org/10.1007/bf01115220.
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Recent reports on the interaction of cardiotoxin and melittin with phospholipid model membranes are reviewed and analyzed. These types of peptide toxins are able to modulate lipid surface curvature and polymorphism in a highly lipid-specific way. It is demonstrated that the remarkable variety of effects of melittin on the organization of different membrane phospholipids can be understood in a relatively simple model, based on the shape-structure concept of lipid polymorphism and taking into account the position of the peptide molecule with respect to the lipids. Based on the strong preference of the peptides for negatively charged lipids and the structural consequences thereof, and on preliminary studies of signal peptide-lipid interaction, a role of inverted or concave lipid structures in the process of protein translocation across membranes is suggested.
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Ghanbarpour, Alireza, Diana P. Valverde, Thomas J. Melia, and Karin M. Reinisch. "A model for a partnership of lipid transfer proteins and scramblases in membrane expansion and organelle biogenesis." Proceedings of the National Academy of Sciences 118, no. 16 (April 13, 2021): e2101562118. http://dx.doi.org/10.1073/pnas.2101562118.
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The autophagy protein ATG2, proposed to transfer bulk lipid from the endoplasmic reticulum (ER) during autophagosome biogenesis, interacts with ER residents TMEM41B and VMP1 and with ATG9, in Golgi-derived vesicles that initiate autophagosome formation. In vitro assays reveal TMEM41B, VMP1, and ATG9 as scramblases. We propose a model wherein membrane expansion results from the partnership of a lipid transfer protein, moving lipids between the cytosolic leaflets of apposed organelles, and scramblases that reequilibrate the leaflets of donor and acceptor organelle membranes as lipids are depleted or augmented. TMEM41B and VMP1 are implicated broadly in lipid homeostasis and membrane dynamics processes in which their scrambling activities likely are key.
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Sadžak, Anja, Janez Mravljak, Nadica Maltar-Strmečki, Zoran Arsov, Goran Baranović, Ina Erceg, Manfred Kriechbaum, Vida Strasser, Jan Přibyl, and Suzana Šegota. "The Structural Integrity of the Model Lipid Membrane during Induced Lipid Peroxidation: The Role of Flavonols in the Inhibition of Lipid Peroxidation." Antioxidants 9, no. 5 (May 15, 2020): 430. http://dx.doi.org/10.3390/antiox9050430.
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The structural integrity, elasticity, and fluidity of lipid membranes are critical for cellular activities such as communication between cells, exocytosis, and endocytosis. Unsaturated lipids, the main components of biological membranes, are particularly susceptible to the oxidative attack of reactive oxygen species. The peroxidation of unsaturated lipids, in our case 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), induces the structural reorganization of the membrane. We have employed a multi-technique approach to analyze typical properties of lipid bilayers, i.e., roughness, thickness, elasticity, and fluidity. We compared the alteration of the membrane properties upon initiated lipid peroxidation and examined the ability of flavonols, namely quercetin (QUE), myricetin (MCE), and myricitrin (MCI) at different molar fractions, to inhibit this change. Using Mass Spectrometry (MS) and Fourier Transform Infrared Spectroscopy (FTIR), we identified various carbonyl products and examined the extent of the reaction. From Atomic Force Microscopy (AFM), Force Spectroscopy (FS), Small Angle X-Ray Scattering (SAXS), and Electron Paramagnetic Resonance (EPR) experiments, we concluded that the membranes with inserted flavonols exhibit resistance against the structural changes induced by the oxidative attack, which is a finding with multiple biological implications. Our approach reveals the interplay between the flavonol molecular structure and the crucial membrane properties under oxidative attack and provides insight into the pathophysiology of cellular oxidative injury.
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Subczynski, Witold Karol, Marija Raguz, and Justyna Widomska. "Multilamellar Liposomes as a Model for Biological Membranes: Saturation Recovery EPR Spin-Labeling Studies." Membranes 12, no. 7 (June 26, 2022): 657. http://dx.doi.org/10.3390/membranes12070657.
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EPR spin labeling has been used extensively to study lipids in model membranes to understand their structures and dynamics in biological membranes. The lipid multilamellar liposomes, which are the most commonly used biological membrane model, were prepared using film deposition methods and investigated with the continuous wave EPR technique (T2-sensitive spin-labeling methods). These investigations provided knowledge about the orientation of lipids, their rotational and lateral diffusion, and their rate of flip-flop between bilayer leaflets, as well as profiles of membrane hydrophobicity, and are reviewed in many papers and book chapters. In the early 1980s, the saturation recovery EPR technique was introduced to membrane studies. Numerous T1-sensitive spin-label methods were developed to obtain detailed information about the three-dimensional dynamic membrane structure. T1-sensitive methods are advantageous over T2-sensitive methods because the T1 of spin labels (1–10 μs) is 10 to 1000 times longer than the T2, which allows for studies of membrane dynamics in a longer time–space scale. These investigations used multilamellar liposomes also prepared using the rapid solvent exchange method. Here, we review works in which saturation recovery EPR spin-labeling methods were applied to investigate the properties of multilamellar lipid liposomes, and we discuss their relationships to the properties of lipids in biological membranes.
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Mori, Kenichi, Yosuke Imai, Tsubasa Takaoka, Koji Iwamoto, Hideyoshi Fuji, and Tyuji Hoshino. "2P270 Database of Lipid Membrane Structures : Computational Analyses of Model Membranes(40. Membrane structure,Poster Session,Abstract,Meeting Program of EABS & BSJ 2006)." Seibutsu Butsuri 46, supplement2 (2006): S363. http://dx.doi.org/10.2142/biophys.46.s363_2.
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El-Beyrouthy, Joyce, and Eric Freeman. "Characterizing the Structure and Interactions of Model Lipid Membranes Using Electrophysiology." Membranes 11, no. 5 (April 27, 2021): 319. http://dx.doi.org/10.3390/membranes11050319.
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The cell membrane is a protective barrier whose configuration determines the exchange both between intracellular and extracellular regions and within the cell itself. Consequently, characterizing membrane properties and interactions is essential for advancements in topics such as limiting nanoparticle cytotoxicity. Characterization is often accomplished by recreating model membranes that approximate the structure of cellular membranes in a controlled environment, formed using self-assembly principles. The selected method for membrane creation influences the properties of the membrane assembly, including their response to electric fields used for characterizing transmembrane exchanges. When these self-assembled model membranes are combined with electrophysiology, it is possible to exploit their non-physiological mechanics to enable additional measurements of membrane interactions and phenomena. This review describes several common model membranes including liposomes, pore-spanning membranes, solid supported membranes, and emulsion-based membranes, emphasizing their varying structure due to the selected mode of production. Next, electrophysiology techniques that exploit these structures are discussed, including conductance measurements, electrowetting and electrocompression analysis, and electroimpedance spectroscopy. The focus of this review is linking each membrane assembly technique to the properties of the resulting membrane, discussing how these properties enable alternative electrophysiological approaches to measuring membrane characteristics and interactions.
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Garcke, Harald, Johannes Kampmann, Andreas Rätz, and Matthias Röger. "A coupled surface-Cahn–Hilliard bulk-diffusion system modeling lipid raft formation in cell membranes." Mathematical Models and Methods in Applied Sciences 26, no. 06 (April 12, 2016): 1149–89. http://dx.doi.org/10.1142/s0218202516500275.
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We propose and investigate a model for lipid raft formation and dynamics in biological membranes. The model describes the lipid composition of the membrane and an interaction with cholesterol. To account for cholesterol exchange between cytosol and cell membrane we couple a bulk-diffusion to an evolution equation on the membrane. The latter describes the relaxation dynamics for an energy which takes lipid–phase separation and lipid–cholesterol interaction energy into account. It takes the form of an (extended) Cahn–Hilliard equation. Different laws for the exchange term represent equilibrium and nonequilibrium models. We present a thermodynamic justification, analyze the respective qualitative behavior and derive asymptotic reductions of the model. In particular we present a formal asymptotic expansion near the sharp interface limit, where the membrane is separated into two pure phases of saturated and unsaturated lipids, respectively. Finally we perform numerical simulations and investigate the long-time behavior of the model and its parameter dependence. Both the mathematical analysis and the numerical simulations show the emergence of raft-like structures in the nonequilibrium case whereas in the equilibrium case only macrodomains survive in the long-time evolution.
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Ouberai, Myriam M., Juan Wang, Marcus J. Swann, Celine Galvagnion, Tim Guilliams, Christopher M. Dobson, and Mark E. Welland. "α-Synuclein Senses Lipid Packing Defects and Induces Lateral Expansion of Lipids Leading to Membrane Remodeling." Journal of Biological Chemistry 288, no. 29 (June 5, 2013): 20883–95. http://dx.doi.org/10.1074/jbc.m113.478297.
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There is increasing evidence for the involvement of lipid membranes in both the functional and pathological properties of α-synuclein (α-Syn). Despite many investigations to characterize the binding of α-Syn to membranes, there is still a lack of understanding of the binding mode linking the properties of lipid membranes to α-Syn insertion into these dynamic structures. Using a combination of an optical biosensing technique and in situ atomic force microscopy, we show that the binding strength of α-Syn is related to the specificity of the lipid environment (the lipid chemistry and steric properties within a bilayer structure) and to the ability of the membranes to accommodate and remodel upon the interaction of α-Syn with lipid membranes. We show that this interaction results in the insertion of α-Syn into the region of the headgroups, inducing a lateral expansion of lipid molecules that can progress to further bilayer remodeling, such as membrane thinning and expansion of lipids out of the membrane plane. We provide new insights into the affinity of α-Syn for lipid packing defects found in vesicles of high curvature and in planar membranes with cone-shaped lipids and suggest a comprehensive model of the interaction between α-Syn and lipid bilayers. The ability of α-Syn to sense lipid packing defects and to remodel membrane structure supports its proposed role in vesicle trafficking.
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Zhytniakivska, Olga. "Interactions of Novel Phosphonium Dye with Lipid Bilayers: A Molecular Dynamics Study." 1, no. 1 (March 17, 2022): 77–84. http://dx.doi.org/10.26565/2312-4334-2022-1-11.
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In the present work the 100-ns molecular dynamics simulations (MD) were performed in the CHARMM36m force field using the GROMACS package to estimate the bilayer location and mechanisms of the interaction between the novel phosphonium dye TDV and the model lipid membranes composed of the phosphatidylcholine (PC) and its mixtures with cholesterol (Chol) or/and anionic phospholipid cardiolipin (CL). Varying the dye initial position relative to the membrane midplane, the dye relative orientation and the charge state of the TDV molecule it was found that the one charge form of TDV, which was initially translated to a distance of 20 Å from the membrane midplane along the bilayer normal, readily penetrates deeper into the membrane interior and remains within the lipid bilayer during the entire simulation time. It was revealed that the probe partitioning into the model membranes was accompanied by the reorientation of TDV molecule from perpendicular to nearly parallel to the membrane surface. The analysis of the MD simulation results showed that the lipid bilayer partitioning and location of the one charge form of TDV depend on the membrane composition. The dye binds more rapidly to the neat PC bilayer than to CL- and Chol-containing model membranes. It was found that in the neat PC and CL-containing membranes the one charge TDV resides at the level of carbonyl groups of lipids (the distances ~ 1.1 nm, 1.2 nm and 1.3 nm from the bilayer center for the PC, CL10 and CL20 lipid membranes, respectively), whereas in the Chol-containing membranes the probe is located at the level of glycerol moiety (~ 1.5 nm and 1.6 nm for the Chol30 and CL10/Chol30 lipid membranes, respectively). It was demonstrated that the dye partitioning into the lipid bilayer does not affect the membrane structural properties.
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Silvius, John. "Lipid microdomains in model and biological membranes: how strong are the connections?" Quarterly Reviews of Biophysics 38, no. 4 (November 2005): 373–83. http://dx.doi.org/10.1017/s003358350600415x.
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1. Introduction 3732. Are rafts probable? 3743. Micro-, nano- or ephemeral domains? 3754. How can we reliably assess ‘raft’ composition? 3765. Are rafts plausible? 3796. What more can model systems contribute to ‘raft’ studies? 3817. References 382The concept of ‘lipid rafts’ and related liquid-ordered membrane microdomains has attracted great attention in the field of membrane biology, both as a novel paradigm in models of membrane organization and for the potential importance of such domains in phenomena such as membrane signaling and the differential trafficking of various membrane components. Studies of biological and of model membranes have gone hand in hand in shaping our current picture of the possible organization and functions of liquid-ordered lipid microdomains in membranes. This essay discusses some important current questions concerning the existence and functional importance of lipid microdomains in mammalian cell membranes, and the potential as well as the limitations of using model systems to help to address such questions.
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Knoll, Wolfgang, Ingo Köper, Renate Naumann, and Eva-Kathrin Sinner. "Tethered bimolecular lipid membranes—A novel model membrane platform." Electrochimica Acta 53, no. 23 (October 2008): 6680–89. http://dx.doi.org/10.1016/j.electacta.2008.02.121.
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Tsuchiya, Hironori, and Maki Mizogami. "Interaction of drugs with lipid raft membrane domains as a possible target." Drug Target Insights 14, no. 1 (December 22, 2020): 34–47. http://dx.doi.org/10.33393/dti.2020.2185.
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Introduction: Plasma membranes are not the homogeneous bilayers of uniformly distributed lipids but the lipid complex with laterally separated lipid raft membrane domains, which provide receptor, ion channel and enzyme proteins with a platform. The aim of this article is to review the mechanistic interaction of drugs with membrane lipid rafts and address the question whether drugs induce physicochemical changes in raft-constituting and raft-surrounding membranes.
Methods: Literature searches of PubMed/MEDLINE and Google Scholar databases from 2000 to 2020 were conducted to include articles published in English in internationally recognized journals. Collected articles were independently reviewed by title, abstract and text for relevance.
Results: The literature search indicated that pharmacologically diverse drugs interact with raft model membranes and cellular membrane lipid rafts. They could physicochemically modify functional protein-localizing membrane lipid rafts and the membranes surrounding such domains, affecting the raft organizational integrity with the resultant exhibition of pharmacological activity. Raft-acting drugs were characterized as ones to decrease membrane fluidity, induce liquid-ordered phase or order plasma membranes, leading to lipid raft formation; and ones to increase membrane fluidity, induce liquid-disordered phase or reduce phase transition temperature, leading to lipid raft disruption.
Conclusion: Targeting lipid raft membrane domains would open a new way for drug design and development. Since angiotensin-converting enzyme 2 receptors which are a cell-specific target of and responsible for the cellular entry of novel coronavirus are localized in lipid rafts, agents that specifically disrupt the relevant rafts may be a drug against coronavirus disease 2019.
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Budin, Itay, Tristan de Rond, Yan Chen, Leanne Jade G. Chan, Christopher J. Petzold, and Jay D. Keasling. "Viscous control of cellular respiration by membrane lipid composition." Science 362, no. 6419 (October 25, 2018): 1186–89. http://dx.doi.org/10.1126/science.aat7925.
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Lipid composition determines the physical properties of biological membranes and can vary substantially between and within organisms. We describe a specific role for the viscosity of energy-transducing membranes in cellular respiration. Engineering of fatty acid biosynthesis inEscherichia coliallowed us to titrate inner membrane viscosity across a 10-fold range by controlling the abundance of unsaturated or branched lipids. These fluidizing lipids tightly controlled respiratory metabolism, an effect that can be explained with a quantitative model of the electron transport chain (ETC) that features diffusion-coupled reactions between enzymes and electron carriers (quinones). Lipid unsaturation also modulated mitochondrial respiration in engineered budding yeast strains. Thus, diffusion in the ETC may serve as an evolutionary constraint for lipid composition in respiratory membranes.
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Hanashima, Shinya, Takanori Nakane, and Eiichi Mizohata. "Heavy Atom Detergent/Lipid Combined X-ray Crystallography for Elucidating the Structure-Function Relationships of Membrane Proteins." Membranes 11, no. 11 (October 27, 2021): 823. http://dx.doi.org/10.3390/membranes11110823.
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Membrane proteins reside in the lipid bilayer of biomembranes and the structure and function of these proteins are closely related to their interactions with lipid molecules. Structural analyses of interactions between membrane proteins and lipids or detergents that constitute biological or artificial model membranes are important for understanding the functions and physicochemical properties of membrane proteins and biomembranes. Determination of membrane protein structures is much more difficult when compared with that of soluble proteins, but the development of various new technologies has accelerated the elucidation of the structure-function relationship of membrane proteins. This review summarizes the development of heavy atom derivative detergents and lipids that can be used for structural analysis of membrane proteins and their interactions with detergents/lipids, including their application with X-ray free-electron laser crystallography.
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Zorilă, Bogdan, George Necula, Mihai Radu, and Mihaela Bacalum. "Melittin Induces Local Order Changes in Artificial and Biological Membranes as Revealed by Spectral Analysis of Laurdan Fluorescence." Toxins 12, no. 11 (November 8, 2020): 705. http://dx.doi.org/10.3390/toxins12110705.
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Antimicrobial peptides (AMPs) are a class of molecules widely used in applications on eukaryotic and prokaryotic cells. Independent of the peptide target, all of them need to first pass or interact with the plasma membrane of the cells. In order to have a better image of the peptide action mechanism with respect to the particular features of the membrane it is necessary to better understand the changes induced by AMPs in the membranes. Laurdan, a lipid membrane probe sensitive to polarity changes in the environment, is used in this study for assessing changes induced by melittin, a well-known peptide, both in model and natural lipid membranes. More importantly, we showed that generalized polarization (GP) values are not always efficient or sufficient to properly characterize the changes in the membrane. We proved that a better method to investigate these changes is to use the previously described log-normal deconvolution allowing us to infer other parameters: the difference between the relative areas of elementary peak (ΔSr), and the ratio of elementary peaks areas (Rs). Melittin induced a slight decrease in local membrane fluidity in homogeneous lipid membranes. The addition of cholesterol stabilizes the membrane more in the presence of melittin. An opposite response was observed in the case of heterogeneous lipid membranes in cells, the local order of lipids being diminished. RS proved to be the most sensitive parameter characterizing the local membrane order, allowing us to distinguish among the responses to melittin of both classes of membrane we investigated (liposomes and cellular membranes). Molecular simulation of the melittin pore in homogeneous lipid bilayer suggests that lipids are more closely packed in the proximity of the melittin pore (a smaller area per lipid), supporting the experimental observation.
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Brémaud, Erwan, Cyril Favard, and Delphine Muriaux. "Deciphering the Assembly of Enveloped Viruses Using Model Lipid Membranes." Membranes 12, no. 5 (April 19, 2022): 441. http://dx.doi.org/10.3390/membranes12050441.
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The cell plasma membrane is mainly composed of phospholipids, cholesterol and embedded proteins, presenting a complex interface with the environment. It maintains a barrier to control matter fluxes between the cell cytosol and its outer environment. Enveloped viruses are also surrounded by a lipidic membrane derived from the host-cell membrane and acquired while exiting the host cell during the assembly and budding steps of their viral cycle. Thus, model membranes composed of selected lipid mixtures mimicking plasma membrane properties are the tools of choice and were used to decipher the first step in the assembly of enveloped viruses. Amongst these viruses, we choose to report the three most frequently studied viruses responsible for lethal human diseases, i.e., Human Immunodeficiency Type 1 (HIV-1), Influenza A Virus (IAV) and Ebola Virus (EBOV), which assemble at the host-cell plasma membrane. Here, we review how model membranes such as Langmuir monolayers, bicelles, large and small unilamellar vesicles (LUVs and SUVs), supported lipid bilayers (SLBs), tethered-bilayer lipid membranes (tBLM) and giant unilamellar vesicles (GUVs) contribute to the understanding of viral assembly mechanisms and dynamics using biophysical approaches.
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Koo, Dong Jun, Tun Naw Sut, Sue Woon Tan, Bo Kyeong Yoon, and Joshua A. Jackman. "Biophysical Characterization of LTX-315 Anticancer Peptide Interactions with Model Membrane Platforms: Effect of Membrane Surface Charge." International Journal of Molecular Sciences 23, no. 18 (September 12, 2022): 10558. http://dx.doi.org/10.3390/ijms231810558.
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LTX-315 is a clinical-stage, anticancer peptide therapeutic that disrupts cancer cell membranes. Existing mechanistic knowledge about LTX-315 has been obtained from cell-based biological assays, and there is an outstanding need to directly characterize the corresponding membrane-peptide interactions from a biophysical perspective. Herein, we investigated the membrane-disruptive properties of the LTX-315 peptide using three cell-membrane-mimicking membrane platforms on solid supports, namely the supported lipid bilayer, intact vesicle adlayer, and tethered lipid bilayer, in combination with quartz crystal microbalance-dissipation (QCM-D) and electrochemical impedance spectroscopy (EIS) measurements. The results showed that the cationic LTX-315 peptide selectively disrupted negatively charged phospholipid membranes to a greater extent than zwitterionic or positively charged phospholipid membranes, whereby electrostatic interactions were the main factor to influence peptide attachment and membrane curvature was a secondary factor. Of note, the EIS measurements showed that the LTX-315 peptide extensively and irreversibly permeabilized negatively charged, tethered lipid bilayers that contained high phosphatidylserine lipid levels representative of the outer leaflet of cancer cell membranes, while circular dichroism (CD) spectroscopy experiments indicated that the LTX-315 peptide was structureless and the corresponding membrane-disruptive interactions did not involve peptide conformational changes. Dynamic light scattering (DLS) measurements further verified that the LTX-315 peptide selectively caused irreversible disruption of negatively charged lipid vesicles. Together, our findings demonstrate that the LTX-315 peptide preferentially disrupts negatively charged phospholipid membranes in an irreversible manner, which reinforces its potential as an emerging cancer immunotherapy and offers a biophysical framework to guide future peptide engineering efforts.
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Mouritsen, Ole G., and Luis A. Bagatolli. "Lipid domains in model membranes: a brief historical perspective." Essays in Biochemistry 57 (February 6, 2015): 1–19. http://dx.doi.org/10.1042/bse0570001.
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All biological membranes consist of a complex composite of macromolecules and macromolecular assemblies, of which the fluid lipid-bilayer component is a core element with regard to cell encapsulation and barrier properties. The fluid lipid bilayer also supports the functional machinery of receptors, channels and pumps that are associated with the membrane. This bilayer is stabilized by weak physical and colloidal forces, and its nature is that of a self-assembled system of amphiphiles in water. Being only approximately 5 nm in thickness and still encapsulating a cell that is three orders of magnitude larger in diameter, the lipid bilayer as a material has very unusual physical properties, both in terms of structure and dynamics. Although the lipid bilayer is a fluid, it has a distinct and structured trans-bilayer profile, and in the plane of the bilayer the various molecular components, viz different lipid species and membrane proteins, have the capacity to organize laterally in terms of differentiated domains on different length and time scales. These elements of small-scale structure and order are crucial for the functioning of the membrane. It has turned out to be difficult to quantitatively study the small-scale structure of biological membranes. A major part of the insight into membrane micro- and nano-domains and the concepts used to describe them have hence come from studies of simple lipid bilayers as models of membranes, by use of a wide range of theoretical, experimental and simulational approaches. Many questions remain to be answered as to which extent the result from model studies can carry over to real biological membranes.
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Sengupta, Prabuddha, and Jennifer Lippincott-Schwartz. "Revisiting Membrane Microdomains and Phase Separation: A Viral Perspective." Viruses 12, no. 7 (July 10, 2020): 745. http://dx.doi.org/10.3390/v12070745.
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Retroviruses selectively incorporate a specific subset of host cell proteins and lipids into their outer membrane when they bud out from the host plasma membrane. This specialized viral membrane composition is critical for both viral survivability and infectivity. Here, we review recent findings from live cell imaging of single virus assembly demonstrating that proteins and lipids sort into the HIV retroviral membrane by a mechanism of lipid-based phase partitioning. The findings showed that multimerizing HIV Gag at the assembly site creates a liquid-ordered lipid phase enriched in cholesterol and sphingolipids. Proteins with affinity for this specialized lipid environment partition into it, resulting in the selective incorporation of proteins into the nascent viral membrane. Building on this and other work in the field, we propose a model describing how HIV Gag induces phase separation of the viral assembly site through a mechanism involving transbilayer coupling of lipid acyl chains and membrane curvature changes. Similar phase-partitioning pathways in response to multimerizing structural proteins likely help sort proteins into the membranes of other budding structures within cells.
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Mouritsen, O. G. "Model Answers to Lipid Membrane Questions." Cold Spring Harbor Perspectives in Biology 3, no. 9 (May 24, 2011): a004622. http://dx.doi.org/10.1101/cshperspect.a004622.
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Takiue, Takanori. "Soft Interfacial Films as a Model for Lipid Raft." MEMBRANE 44, no. 2 (2019): 57–62. http://dx.doi.org/10.5360/membrane.44.57.
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Kleusch, Christian, Cornelia Monzel, Krishna Chander Sridhar, Bernd Hoffmann, Agnes Csiszár, and Rudolf Merkel. "Fluorescence Correlation Spectroscopy Reveals Interaction of Some Microdomain-Associated Lipids with Cellular Focal Adhesion Sites." International Journal of Molecular Sciences 21, no. 21 (October 31, 2020): 8149. http://dx.doi.org/10.3390/ijms21218149.
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Cells adhere to the extracellular matrix at distinct anchoring points, mostly focal adhesions. These are rich in immobile transmembrane- and cytoskeletal-associated proteins, some of which are known to interact with lipids of the plasma membrane. To investigate their effect on lipid mobility and molecular interactions, fluorescently labeled lipids were incorporated into the plasma membranes of primary myofibroblasts using fusogenic liposomes. With fluorescence correlation spectroscopy, we tested mobilities of labeled microdomain-associated lipids such as sphingomyelin (SM), ganglioside (GM1), and cholesterol as well as of a microdomain-excluded phospholipid (PC) and a lipid-like molecule (DiIC18(7)) in focal adhesions (FAs) and in neighboring non-adherent membrane areas. We found significantly slower diffusion of SM and GM1 inside FAs but no effect on cholesterol, PC, and DiIC18(7). These data were compared to the molecular behavior in Lo/Ld-phase separated giant unilamellar vesicles, which served as a model system for microdomain containing lipid membranes. In contrast to the model system, lipid mobility changes in FAs were molecularly selective, and no particle enrichment occurred. Our findings suggest that lipid behavior in FAs cannot be described by Lo/Ld-phase separation. The observed slow-down of some molecules in FAs is potentially due to transient binding between lipids and some molecular constituent(s).
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Li, Shiqi, Ruohua Ren, Letian Lyu, Jiangning Song, Yajun Wang, Tsung-Wu Lin, Anton Le Brun, Hsien-Yi Hsu, and Hsin-Hui Shen. "Solid and Liquid Surface-Supported Bacterial Membrane Mimetics as a Platform for the Functional and Structural Studies of Antimicrobials." Membranes 12, no. 10 (September 20, 2022): 906. http://dx.doi.org/10.3390/membranes12100906.
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Increasing antibiotic resistance has provoked the urgent need to investigate the interactions of antimicrobials with bacterial membranes. The reasons for emerging antibiotic resistance and innovations in novel therapeutic approaches are highly relevant to the mechanistic interactions between antibiotics and membranes. Due to the dynamic nature, complex compositions, and small sizes of native bacterial membranes, bacterial membrane mimetics have been developed to allow for the in vitro examination of structures, properties, dynamics, and interactions. In this review, three types of model membranes are discussed: monolayers, supported lipid bilayers, and supported asymmetric bilayers; this review highlights their advantages and constraints. From monolayers to asymmetric bilayers, biomimetic bacterial membranes replicate various properties of real bacterial membranes. The typical synthetic methods for fabricating each model membrane are introduced. Depending on the properties of lipids and their biological relevance, various lipid compositions have been used to mimic bacterial membranes. For example, mixtures of phosphatidylethanolamines (PE), phosphatidylglycerols (PG), and cardiolipins (CL) at various molar ratios have been used, approaching actual lipid compositions of Gram-positive bacterial membranes and inner membranes of Gram-negative bacteria. Asymmetric lipid bilayers can be fabricated on solid supports to emulate Gram-negative bacterial outer membranes. To probe the properties of the model bacterial membranes and interactions with antimicrobials, three common characterization techniques, including quartz crystal microbalance with dissipation (QCM-D), surface plasmon resonance (SPR), and neutron reflectometry (NR) are detailed in this review article. Finally, we provide examples showing that the combination of bacterial membrane models and characterization techniques is capable of providing crucial information in the design of new antimicrobials that combat bacterial resistance.
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Elderdfi, M., and A. F. Sikorski. "Interaction of membrane palmitoylated protein-1 with model lipid membranes." General physiology and biophysics 37, no. 06 (2018): 603–17. http://dx.doi.org/10.4149/gpb_2018029.
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Favard, Cyril, Jakub Chojnacki, Naresh Yandrapalli, Johnson Mak, Christian Eggeling, and Delphine Muriaux. "Specific Lipid Recruitment by the Retroviral Gag Protein upon HIV-1 Assembly: From Model Membranes to Infected Cells." Proceedings 50, no. 1 (June 24, 2020): 102. http://dx.doi.org/10.3390/proceedings2020050102.
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The retroviral Gag protein targets the plasma membrane of infected cells for viral particle formation and release. The matrix domain (MA) of Gag is myristoylated for membrane anchoring but also contains a highly basic region that recognizes acidic phospholipids. Gag targets lipid molecules at the inner leaflet of the plasma membrane including phosphatidylinositol (4,5) bisphosphate (PI(4,5)P2) and cholesterol. Here, we addressed the question whether HIV-1 Gag was able to trap PI(4,5)P2 and/or other lipids during HIV-1 assembly in silico, in vitro on reconstituted membranes and in cellulo at the plasma membrane of the host CD4+ T cells. In silico, we could observe the first PI(4,5)P2 preferential recruitment by HIV-1 MA or Gag while protein docked on artificial membranes. In vitro, using biophysical techniques, we observed the specific trapping of PI(4,5)P2, and, to a lesser extent, cholesterol and the exclusion of sphingomyelin, during HIV-1 myr(-)Gag self-assembly on LUVs and SLBs. Finally, in infected living CD4+ T cells, we measured lipid dynamics within and away from HIV-1 assembly sites using super-resolution stimulated emission depletion (STED) microscopy coupled with scanning Fluorescence Correlation Spectroscopy (sSTED-FCS). The analysis of HIV-1 infected CD4+ T lymphocytes revealed that, upon virus assembly, HIV-1 is able to specifically trap PI(4,5)P2, and cholesterol but not phosphatidylethanolamine (PE) or sphingomyelin (SM) at the cellular membrane. Furthermore, analyzing CD4+ T cells expressing only HIV-1 Gag protein showed that Gag is the main driving force restricting the mobility of PI(4,5)P2 and cholesterol at the cell plasma membrane. Our data provide the first direct evidence showing that HIV-1 Gag creates its own specific lipid environment for virus assembly by selectively recruiting lipids to generate PI(4,5)P2/cholesterol-enriched nanodomains favoring virus assembly, and that HIV-1 does not assemble on pre-existing lipid domains.
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Tukova, Anastasiia, and Alison Rodger. "Spectroscopy of model-membrane liposome-protein systems: complementarity of linear dichroism, circular dichroism, fluorescence and SERS." Emerging Topics in Life Sciences 5, no. 1 (May 4, 2021): 61–75. http://dx.doi.org/10.1042/etls20200354.
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A range of membrane models have been developed to study components of cellular systems. Lipid vesicles or liposomes are one such artificial membrane model which mimics many properties of the biological system: they are lipid bilayers composed of one or more lipids to which other molecules can associate. Liposomes are thus ideal to study the roles of cellular lipids and their interactions with other membrane components to understand a wide range of cellular processes including membrane disruption, membrane transport and catalytic activity. Although liposomes are much simpler than cellular membranes, they are still challenging to study and a variety of complementary techniques are needed. In this review article, we consider several currently used analytical methods for spectroscopic measurements of unilamellar liposomes and their interaction with proteins and peptides. Among the variety of spectroscopic techniques seeing increasing application, we have chosen to discuss: fluorescence based techniques such as FRET (fluorescence resonance energy transfer) and FRAP (fluorescence recovery after photobleaching), that are used to identify localisation and dynamics of molecules in the membrane; circular dichroism (CD) and linear dichroism (LD) for conformational and orientation changes of proteins on membrane binding; and SERS (Surface Enhanced Raman Spectroscopy) as a rapidly developing ultrasensitive technique for site-selective molecular characterisation. The review contains brief theoretical basics of the listed techniques and recent examples of their successful applications for membrane studies.
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Efimova, S. S., T. E. Tertychnaya, S. N. Lavrenov, and O. S. Ostroumova. "The Mechanisms of Action of Triindolylmethane Derivatives on Lipid Membranes." Acta Naturae 11, no. 3 (September 15, 2019): 38–45. http://dx.doi.org/10.32607/20758251-2019-11-3-38-45.
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The effects of new synthetic antibacterial agents - tris(1-pentyl-1H-indol-3-yl)methylium chloride (LCTA-1975) and (1-(4-(dimethylamino)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)-1H-indol-3-yl)bis(1-propyl- 1H-indol-3-yl)methylium chloride (LCTA-2701 - on model lipid membranes were studied. The ability of the tested agents to form ion-conductive transmembrane pores, influence the electrical stability of lipid bilayers and the phase transition of membrane lipids, and cause the deformation and fusion of lipid vesicles was investigated. It was established that both compounds exert a strong detergent effect on model membranes. The results of differential scanning microcalorimetry and measuring of the threshold transmembrane voltage that caused membrane breakdown before and after adsorption of LCTA-1975 and LCTA-2701 indicated that both agents cause disordering of membrane lipids. Synergism of the uncoupling action of antibiotics and the alkaloid capsaicin on model lipid membranes was shown. The threshold concentration of the antibiotic that caused an increase in the ion permeability of the lipid bilayer depended on the membrane lipid composition. It was lower by an order of magnitude in the case of negatively charged lipid bilayers than for the uncharged membranes. This can be explained by the positive charge of the tested agents. At the same time, LCTA-2701 was characterized by greater efficiency than LCTA-1975. In addition to its detergent action, LCTA-2701 can induce ion-permeable transmembrane pores: step-like current fluctuations corresponding to the opening and closing of individual ion channels were observed. The difference in the mechanisms of action might be related to the structural features of the antibiotic molecules: in the LCTA-1975 molecule, all three substituents at the nitrogen atoms of the indole rings are identical and represent n-alkyl (pentyl) groups, while LCTA-2701 contains a maleimide group, along with two alkyl substituents (n-propyl). The obtained results might be relevant to our understanding of the mechanism of action of new antibacterial agents, explaining the difference in the selectivity of action of the tested agents on the target microorganisms and their toxicity to human cells. Model lipid membranes should be used in further studies of the trends in the modification and improvement of the structures of new antibacterial agents.
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Lowry, Troy W., Aubrey E. Kusi-Appiah, Debra Ann Fadool, and Steven Lenhert. "Odor Discrimination by Lipid Membranes." Membranes 13, no. 2 (January 24, 2023): 151. http://dx.doi.org/10.3390/membranes13020151.
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Odor detection and discrimination in mammals is known to be initiated by membrane-bound G-protein-coupled receptors (GPCRs). The role that the lipid membrane may play in odor discrimination, however, is less well understood. Here, we used model membrane systems to test the hypothesis that phospholipid bilayer membranes may be capable of odor discrimination. The effect of S-carvone, R-carvone, and racemic lilial on the model membrane systems was investigated. The odorants were found to affect the fluidity of supported lipid bilayers as measured by fluorescence recovery after photobleaching (FRAP). The effect of odorants on surface-supported lipid multilayer microarrays of different dimensions was also investigated. The lipid multilayer micro- and nanostructure was highly sensitive to exposure to these odorants. Fluorescently-labeled lipid multilayer droplets of 5-micron diameter were more responsive to these odorants than ethanol controls. Arrays of lipid multilayer diffraction gratings distinguished S-carvone from R-carvone in an artificial nose assay. Our results suggest that lipid bilayer membranes may play a role in odorant discrimination and molecular recognition in general.
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Vogel, Alexander, Jörg Nikolaus, Katrin Weise, Gemma Triola, Herbert Waldmann, Roland Winter, Andreas Herrmann, and Daniel Huster. "Interaction of the human N-Ras protein with lipid raft model membranes of varying degrees of complexity." Biological Chemistry 395, no. 7-8 (July 1, 2014): 779–89. http://dx.doi.org/10.1515/hsz-2013-0294.
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Abstract Ternary lipid mixtures composed of cholesterol, saturated (frequently with sphingosine backbone), and unsaturated phospholipids show stable phase separation and are often used as model systems of lipid rafts. Yet, their ability to reproduce raft properties and function is still debated. We investigated the properties and functional aspects of three lipid raft model systems of varying degrees of biological relevance – PSM/POPC/Chol, DPPC/POPC/Chol, and DPPC/DOPC/Chol – using 2H solid-state nuclear magnetic resonance (NMR) spectroscopy, fluorescence microscopy, and atomic force microscopy. While some minor differences were observed, the general behavior and properties of all three model mixtures were similar to previously investigated influenza envelope lipid membranes, which closely mimic the lipid composition of biological membranes. For the investigation of the functional aspects, we employed the human N-Ras protein, which is posttranslationally modified by two lipid modifications that anchor the protein to the membrane. It was previously shown that N-Ras preferentially resides in liquid-disordered domains and exhibits a time-dependent accumulation in the domain boundaries of influenza envelope lipid membranes. For all three model mixtures, we observed the same membrane partitioning behavior for N-Ras. Therefore, we conclude that even relatively simple models of raft membranes are able to reproduce many of their specific properties and functions.
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Swana, Kathleen W., Ramanathan Nagarajan, and Terri A. Camesano. "Atomic Force Microscopy to Characterize Antimicrobial Peptide-Induced Defects in Model Supported Lipid Bilayers." Microorganisms 9, no. 9 (September 17, 2021): 1975. http://dx.doi.org/10.3390/microorganisms9091975.
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Antimicrobial peptides (AMPs) interact with bacterial cell membranes through a variety of mechanisms, causing changes extending from nanopore formation to microscale membrane lysis, eventually leading to cell death. Several AMPs also disrupt mammalian cell membranes, despite their significantly different lipid composition and such collateral hemolytic damage hinders the potential therapeutic applicability of the AMP as an anti-microbial. Elucidating the mechanisms underlying the AMP–membrane interactions is challenging due to the variations in the chemical and structural features of the AMPs, the complex compositional variations of cell membranes and the inadequacy of any single experimental technique to comprehensively probe them. (1) Background: Atomic Force Microscopy (AFM) imaging can be used in combination with other techniques to help understand how AMPs alter the orientation and structural organization of the molecules within cell membranes exposed to AMPs. The structure, size, net charge, hydrophobicity and amphipathicity of the AMPs affect how they interact with cell membranes of differing lipid compositions. (2) Methods: Our study examined two different types of AMPs, a 20-amino acid, neutral, α-helical (amphipathic) peptide, alamethicin, and a 13-amino acid, non-α-helical cationic peptide, indolicidin (which intramolecularly folds, creating a hydrophobic core), for their interactions with supported lipid bilayers (SLBs). Robust SLB model membranes on quartz supports, incorporating predominantly anionic lipids representative of bacterial cells, are currently not available and remain to be developed. Therefore, the SLBs of zwitterionic egg phosphatidylcholine (PC), which represents the composition of a mammalian cell membrane, was utilized as the model membrane. This also allows for a comparison with the results obtained from the Quartz Crystal Microbalance with Dissipation (QCM-D) experiments conducted for these peptides interacting with the same zwitterionic SLBs. Further, in the case of alamethicin, because of its neutrality, the lipid charge may be less relevant for understanding its membrane interactions. (3) Results: Using AFM imaging and roughness analysis, we found that alamethicin produced large, unstable defects in the membrane at 5 µM concentrations, and completely removed the bilayer at 10 µM. Indolicidin produced smaller holes in the bilayer at 5 and 10 µM, although they were able to fill in over time. The root-mean-square (RMS) roughness values for the images showed that the surface roughness caused by visible defects peaked after peptide injection and gradually decreased over time. (4) Conclusions: AFM is useful for helping to uncover the dynamic interactions between different AMPs and cell membranes, which can facilitate the selection and design of more efficient AMPs for use in therapeutics and antimicrobial applications.
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Tavares, G. D., M. C. de Oliveira, J. M. C. Vilela, and M. S. Andrade. "Deposition of Lipid Bilayers with Atomic Force Microscopy." Microscopy and Microanalysis 11, S03 (December 2005): 44–47. http://dx.doi.org/10.1017/s1431927605050853.
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Biological membranes are constituted of lipids organized as a two dimensional bilayer supporting peripheral and integral proteins, providing a barrier between the inside and the outside of a cell [1]. Similar membranes can be prepared from the lipid mixtures forming liposomes. The liposomes are multi or unilamellar spherical vesicles in which an aqueous volume is enclosed and can be used to encapsulate some drugs [2]. In order to better expose the details of their structure, these membranes are generally deposited on the surface of a flat substrate. These supported planar lipid membranes can also provide a model system for investigating the properties and functions of the complex cell membrane and membrane mediated processes such as recognition events and biological signal transduction. Various methods have been used to create artificial lipid membranes supported on a solid surface, being the most used the Langmuir-Blodgett monolayers formation [3], the vesicle fusion or liposome adsorption [4] and the solution spreading [5].
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Hill, Reghan J., and Chih-Ying Wang. "Diffusion in phospholipid bilayer membranes: dual-leaflet dynamics and the roles of tracer–leaflet and inter-leaflet coupling." Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences 470, no. 2167 (July 8, 2014): 20130843. http://dx.doi.org/10.1098/rspa.2013.0843.
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A variety of observations—sometimes controversial—have been made in recent decades when attempting to elucidate the roles of interfacial slip on tracer diffusion in phospholipid membranes. Evans–Sackmann theory (1988) has furnished membrane viscosities and lubrication-film thicknesses for supported membranes from experimentally measured lateral diffusion coefficients. Similar to the Saffman and Delbrück model, which is the well-known counterpart for freely supported membranes, the bilayer is modelled as a single two-dimensional fluid. However, the Evans–Sackman model cannot interpret the mobilities of monotopic tracers, such as individual lipids or rigidly bound lipid assemblies; neither does it account for tracer–leaflet and inter-leaflet slip. To address these limitations, we solve the model of Wang and Hill, in which two leaflets of a bilayer membrane, a circular tracer and supports are coupled by interfacial friction, using phenomenological friction/slip coefficients. This furnishes an exact solution that can be readily adopted to interpret the mobilities of a variety of mosaic elements—including lipids, integral monotopic and polytopic proteins, and lipid rafts—in supported bilayer membranes.
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POLYANSKY, ANTON A., PAVEL E. VOLYNSKY, and ROMAN G. EFREMOV. "COMPUTER SIMULATIONS OF MEMBRANE-LYTIC PEPTIDES: PERSPECTIVES IN DRUG DESIGN." Journal of Bioinformatics and Computational Biology 05, no. 02b (April 2007): 611–26. http://dx.doi.org/10.1142/s0219720007002783.
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Structure activity relationships were investigated for membrane-lytic peptides (MLP) Ltc1 and Ltc2a from the latarcin family. The peptides were studied via long-term molecular dynamics (MD) simulations in different membrane environments (detergent micelles, mixed lipid bilayers mimiking eukaryotic and bacterial membranes). The calculated structure of Ltc2a in sodium dodecyl sulfate micelle agrees well with the data obtained by 1H-NMR spectroscopy. This validates the applied modeling approach. The binding mode of MLPs is governed by several factors: (i) the membrane surface curvature; (ii) the conformational plasticity and hydrophobic organization of the peptide, which depend on the arrangement of charged, non-polar and helix-breaking residues in the amino acid sequence. In contrast to Ltc1, insertion of Ltc2a into model membranes induces significant changes in dynamic behavior of lipids in the contact region. Such a prominent membrane destabilization correlates with high membrane-lytic activity of Ltc2a. In all cases the "membrane response" has a local character and is caused by formation of specific peptide-lipid contacts. Results of MD simulations of Ltc2a in model membranes were used to develop a number of its analogs with predefined activity.
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Kamiya, Koki. "Development of Artificial Cell Models Using Microfluidic Technology and Synthetic Biology." Micromachines 11, no. 6 (May 30, 2020): 559. http://dx.doi.org/10.3390/mi11060559.
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Giant lipid vesicles or liposomes are primarily composed of phospholipids and form a lipid bilayer structurally similar to that of the cell membrane. These vesicles, like living cells, are 5–100 μm in diameter and can be easily observed using an optical microscope. As their biophysical and biochemical properties are similar to those of the cell membrane, they serve as model cell membranes for the investigation of the biophysical or biochemical properties of the lipid bilayer, as well as its dynamics and structure. Investigation of membrane protein functions and enzyme reactions has revealed the presence of soluble or membrane proteins integrated in the giant lipid vesicles. Recent developments in microfluidic technologies and synthetic biology have enabled the development of well-defined artificial cell models with complex reactions based on the giant lipid vesicles. In this review, using microfluidics, the formations of giant lipid vesicles with asymmetric lipid membranes or complex structures have been described. Subsequently, the roles of these biomaterials in the creation of artificial cell models including nanopores, ion channels, and other membrane and soluble proteins have been discussed. Finally, the complex biological functions of giant lipid vesicles reconstituted with various types of biomolecules has been communicated. These complex artificial cell models contribute to the production of minimal cells or protocells for generating valuable or rare biomolecules and communicating between living cells and artificial cell models.
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Kelley, Elizabeth G., Moritz P. K. Frewein, Orsolya Czakkel, and Michihiro Nagao. "Nanoscale Bending Dynamics in Mixed-Chain Lipid Membranes." Symmetry 15, no. 1 (January 9, 2023): 191. http://dx.doi.org/10.3390/sym15010191.
Full textAbstract:
Lipids that have two tails of different lengths are found throughout biomembranes in nature, yet the effects of this asymmetry on the membrane properties are not well understood, especially when it comes to the membrane dynamics. Here we study the nanoscale bending fluctuations in model mixed-chain 14:0–18:0 PC (MSPC) and 18:0–14:0 PC (SMPC) lipid bilayers using neutron spin echo (NSE) spectroscopy. We find that despite the partial interdigitation that is known to persist in the fluid phase of these membranes, the collective fluctuations are enhanced on timescales of tens of nanoseconds, and the chain-asymmetric lipid bilayers are softer than an analogous chain-symmetric lipid bilayer with the same average number of carbons in the acyl tails, di-16:0 PC (DPPC). Quantitative comparison of the NSE results suggests that the enhanced bending fluctuations at the nanosecond timescales are consistent with experimental and computational studies that showed the compressibility moduli of chain-asymmetric lipid membranes are 20% to 40% lower than chain-symmetric lipid membranes. These studies add to growing evidence that the partial interdigitation in mixed-chain lipid membranes is highly dynamic in the fluid phase and impacts membrane dynamic processes from the molecular to mesoscopic length scales without significantly changing the bilayer thickness or area per lipid.
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Day, Charles A., and Anne K. Kenworthy. "Functions of cholera toxin B-subunit as a raft cross-linker." Essays in Biochemistry 57 (February 6, 2015): 135–45. http://dx.doi.org/10.1042/bse0570135.
Full textAbstract:
Lipid rafts are putative complexes of lipids and proteins in cellular membranes that are proposed to function in trafficking and signalling events. CTxB (cholera toxin B-subunit) has emerged as one of the most studied examples of a raft-associated protein. Consisting of the membrane-binding domain of cholera toxin, CTxB binds up to five copies of its lipid receptor on the plasma membrane of the host cell. This multivalency of binding gives the toxin the ability to reorganize underlying membrane structure by cross-linking otherwise small and transient lipid rafts. CTxB thus serves as a useful model for understanding the properties and functions of protein-stabilized domains. In the present chapter, we summarize current evidence that CTxB associates with and cross-links lipid rafts, discuss how CTxB binding modulates the architecture and dynamics of membrane domains, and describe the functional consequences of this cross-linking behaviour on toxin uptake into cells via endocytosis.
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Pullmannová, Petra, Elena Ermakova, Andrej Kováčik, Lukáš Opálka, Jaroslav Maixner, Jarmila Zbytovská, Norbert Kučerka, and Kateřina Vávrová. "Long and very long lamellar phases in model stratum corneum lipid membranes." Journal of Lipid Research 60, no. 5 (March 18, 2019): 963–71. http://dx.doi.org/10.1194/jlr.m090977.
Full textAbstract:
Membrane models of the stratum corneum (SC) lipid barrier, either healthy or affected by recessive X-linked ichthyosis, constructed from ceramide [Cer; nonhydroxyacyl sphingosine N-tetracosanoyl-d-erythro-sphingosine (CerNS24) alone or with omega-O-acylceramide N-(32-linoleyloxy)dotriacontanoyl-d-erythro-sphingosine (CerEOS)], FFAs(C16–24), cholesterol (Chol), and sodium cholesteryl sulfate (CholS) were investigated. X-ray diffraction (XRD) revealed a previously unreported polymorphism of the membranes. In the absence of CerEOS, the membranes formed a short lamellar phase (SLP; the repeat distance d = 5.3 nm), a medium lamellar phase (MLP; d = 10.6 nm), or very long lamellar phases (VLLP; d = 15.9 and 21.2 nm). An increased CholS-to-Chol ratio modulated the membrane polymorphism, although the CholS phase separated at ≥ 7 weight% (of total lipids). The presence of CerEOS led to the stable long lamellar phase (LLP) with d = 12.2 nm and prevented VLLP formation. Our XRD results agree well with recently published cryo-electron microscopy data for vitreous skin sections, while also revealing new structures. Thus, lamellar phases with long repeat distances (MLP and VLLP) may be formed in the absence of omega-O-acylceramide, whereas these ultralong Cer species likely stabilize the final SC lipid architecture of LLP by riveting the adjacent lipid layers.