Special Issue "Cellular Membrane Domains and Organization"

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: closed (30 July 2018)

Special Issue Editors

Guest Editor
Dr. Nadège Jamin

Institute for Integrative Biology of the Cell (I2BC), Institut des Sciences du Vivant Frédéric Joliot, SB2SM/LPSM, CEA, CNRS UMR9198, Université Paris-Sud, Centre de Saclay, 91191 Gif-sur-Yvette cedex, France
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Interests: protein–lipid interactions; caveolin; structural analysis of membrane proteins
Guest Editor
Dr. Stéphane Orlowski

Institute for Integrative Biology of the Cell (I2BC), Institut des Sciences du Vivant Frédéric Joliot, SB2SM/LPSM, CEA, CNRS UMR9198, Université Paris-Sud, Centre de Saclay, 91191 Gif-sur-Yvette cedex, France
Website | E-Mail
Interests: membrane transporters enzymology; ABC proteins; P-glycoprotein; cholesterol transport; fluorescent cholesterol probes

Special Issue Information

Dear Colleagues, 

Biological membranes are one of the bases of life, as they establish structural frontiers within cells and between cells and their environment, this compartmentalization, being accompanied by various biochemical opportunities thanks to the anisotropy they provide within the surrounding extra and intracellular reaction medium. In addition, the inherent bi-dimensionality of membranes also includes another level of anisotropy by presenting various heterogeneities. Indeed, it appears now more and more convincingly that lateral heterogeneity, made of membrane lipid domains, along with transversal heterogeneity, consisting in both general and local asymmetry of the bilayer, are relevant and important features of membrane organization, in both structural and functional perspectives. Although lipid domains are an intrinsic property of lipid mixtures, they lead to pivotal functional repercussions in cell physiology due to the involvement of membrane proteins. In fact, relevancy of membrane domains uncovers at least three integration levels, with (i) at molecular level, lipid–protein specific interactions modulating biochemical activity of a receptor or a transporter, (ii) at membrane level, protein segregation and protein–protein interactions modulating their effects in a signaling cascade, (iii) at cellular level, local induction of membrane curvature leading to endocytosis or vesicle secretion, only to mention few typical examples. However, in biological membranes, the seminal question to know which of lipids and proteins are responsible for the driving force for membrane domains formation and regulation has a dual answer, with entangled and mutual roles for both of them. Even in some cases where a “marker” protein has been reported (the most well-known example being caveolin for caveolae), it is not straightforward to determine whether this protein has a role of formation inducer, structure stabilizer, or functional effector. In particular, a remarkable property of membrane domains is their diversity of nature, mainly in term of size, lifetime, and lipid and protein composition. Additionally, and likely as a consequence, another trait of membrane domains is the large variety of experimental approaches and technical tools devoted to evidence and study them.

Clearly, the field of membrane lipid domains is rich and complex, and thus so fascinating. This field of research witnesses the achievement of a modern view of membrane biophysics and biology, but it also leads to numerous questions associated with these new concepts. It is thus expected that the various contributions in this Special Issue will shed attractive and stimulating new light on various aspects of this multidisciplinary and exciting field of research, subjected to intense investigational efforts that now go from mammalian cells to other kingdoms of life such as fungi/yeasts, plants and bacteria.

Dr. Nadège Jamin
Dr. Stéphane Orlowski
Guest Editors

Manuscript Submission Information

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Keywords

  • lipid domains
  • membrane organization
  • lateral and transversal heterogeneities
  • membrane protein segregation
  • lipid-protein interactions
  • detergent-resistant membranes
  • membrane rafts
  • caveolae
  • membrane curvature and budding
  • membrane regulation of signaling cascades

Published Papers (9 papers)

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Research

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Open AccessArticle Numerical Simulation and FRAP Experiments Show That the Plasma Membrane Binding Protein PH-EFA6 Does Not Exhibit Anomalous Subdiffusion in Cells
Biomolecules 2018, 8(3), 90; https://doi.org/10.3390/biom8030090
Received: 18 July 2018 / Revised: 27 August 2018 / Accepted: 28 August 2018 / Published: 5 September 2018
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Abstract
The fluorescence recovery after photobleaching (FRAP) technique has been used for decades to measure movements of molecules in two-dimension (2D). Data obtained by FRAP experiments in cell plasma membranes are assumed to be described through a means of two parameters, a diffusion coefficient,
[...] Read more.
The fluorescence recovery after photobleaching (FRAP) technique has been used for decades to measure movements of molecules in two-dimension (2D). Data obtained by FRAP experiments in cell plasma membranes are assumed to be described through a means of two parameters, a diffusion coefficient, D (as defined in a pure Brownian model) and a mobile fraction, M. Nevertheless, it has also been shown that recoveries can be nicely fit using anomalous subdiffusion. Fluorescence recovery after photobleaching (FRAP) at variable radii has been developed using the Brownian diffusion model to access geometrical characteristics of the surrounding landscape of the molecule. Here, we performed numerical simulations of continuous time random walk (CTRW) anomalous subdiffusion and interpreted them in the context of variable radii FRAP. These simulations were compared to experimental data obtained at variable radii on living cells using the pleckstrin homology (PH) domain of the membrane binding protein EFA6 (exchange factor for ARF6, a small G protein). This protein domain is an excellent candidate to explore the structure of the interface between cytosol and plasma membrane in cells. By direct comparison of our numerical simulations to the experiments, we show that this protein does not exhibit anomalous diffusion in baby hamster kidney (BHK) cells. The non Brownian PH-EFA6 dynamics observed here are more related to spatial heterogeneities such as cytoskeleton fence effects. Full article
(This article belongs to the Special Issue Cellular Membrane Domains and Organization)
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Open AccessArticle Determination of the Membrane Environment of CD59 in Living Cells
Biomolecules 2018, 8(2), 28; https://doi.org/10.3390/biom8020028
Received: 15 March 2018 / Revised: 24 April 2018 / Accepted: 14 May 2018 / Published: 17 May 2018
Cited by 1 | PDF Full-text (1299 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The organization and dynamics of proteins and lipids in the plasma membrane, and their role in membrane functionality, have been subject of a long-lasting debate. Specifically, it is unclear to what extent membrane proteins are affected by their immediate lipid environment and vice
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The organization and dynamics of proteins and lipids in the plasma membrane, and their role in membrane functionality, have been subject of a long-lasting debate. Specifically, it is unclear to what extent membrane proteins are affected by their immediate lipid environment and vice versa. Studies on model membranes and plasma membrane vesicles indicated preferences of proteins for lipid phases characterized by different acyl chain order; however, whether such phases do indeed exist in live cells is still not known. Here, we refine a previously developed micropatterning approach combined with single molecule tracking to quantify the influence of the glycosylphosphatidylinositol-anchored (GPI-anchored) protein CD59 on its molecular environment directly in the live cell plasma membrane. We find that locally enriched and immobilized CD59 presents obstacles to the diffusion of fluorescently labeled lipids with a different phase-partitioning behavior independent of cell cholesterol levels and type of lipid. Our results give no evidence for either specific binding of the lipids to CD59 or the existence of nanoscopic ordered membrane regions associated with CD59. Full article
(This article belongs to the Special Issue Cellular Membrane Domains and Organization)
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Open AccessFeature PaperArticle Membrane Remodeling as a Key Player of the Hepatotoxicity Induced by Co-Exposure to Benzo[a]pyrene and Ethanol of Obese Zebrafish Larvae
Biomolecules 2018, 8(2), 26; https://doi.org/10.3390/biom8020026
Received: 6 April 2018 / Revised: 4 May 2018 / Accepted: 4 May 2018 / Published: 14 May 2018
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Abstract
The rise in prevalence of non-alcoholic fatty liver disease (NAFLD) constitutes an important public health concern worldwide. Including obesity, numerous risk factors of NAFLD such as benzo[a]pyrene (B[a]P) and ethanol have been identified as modifying the physicochemical properties of the plasma membrane in
[...] Read more.
The rise in prevalence of non-alcoholic fatty liver disease (NAFLD) constitutes an important public health concern worldwide. Including obesity, numerous risk factors of NAFLD such as benzo[a]pyrene (B[a]P) and ethanol have been identified as modifying the physicochemical properties of the plasma membrane in vitro thus causing membrane remodeling—changes in membrane fluidity and lipid-raft characteristics. In this study, the possible involvement of membrane remodeling in the in vivo progression of steatosis to a steatohepatitis-like state upon co-exposure to B[a]P and ethanol was tested in obese zebrafish larvae. Larvae bearing steatosis as the result of a high-fat diet were exposed to ethanol and/or B[a]P for seven days at low concentrations coherent with human exposure in order to elicit hepatotoxicity. In this condition, the toxicant co-exposure raised global membrane order with higher lipid-raft clustering in the plasma membrane of liver cells, as evaluated by staining with the fluoroprobe di-4-ANEPPDHQ. Involvement of this membrane’s remodeling was finally explored by using the lipid-raft disruptor pravastatin that counteracted the effects of toxicant co-exposure both on membrane remodeling and toxicity. Overall, it can be concluded that B[a]P/ethanol co-exposure can induce in vivo hepatotoxicity via membrane remodeling which could be considered as a good target mechanism for developing combination therapy to deal with steatohepatitis. Full article
(This article belongs to the Special Issue Cellular Membrane Domains and Organization)
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Review

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Open AccessReview Plasma Membrane Lipid Domains as Platforms for Vesicle Biogenesis and Shedding?
Biomolecules 2018, 8(3), 94; https://doi.org/10.3390/biom8030094
Received: 5 August 2018 / Revised: 3 September 2018 / Accepted: 4 September 2018 / Published: 14 September 2018
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Abstract
Extracellular vesicles (EVs) contribute to several pathophysiological processes and appear as emerging targets for disease diagnosis and therapy. However, successful translation from bench to bedside requires deeper understanding of EVs, in particular their diversity, composition, biogenesis and shedding mechanisms. In this review, we
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Extracellular vesicles (EVs) contribute to several pathophysiological processes and appear as emerging targets for disease diagnosis and therapy. However, successful translation from bench to bedside requires deeper understanding of EVs, in particular their diversity, composition, biogenesis and shedding mechanisms. In this review, we focus on plasma membrane-derived microvesicles (MVs), far less appreciated than exosomes. We integrate documented mechanisms involved in MV biogenesis and shedding, focusing on the red blood cell as a model. We then provide a perspective for the relevance of plasma membrane lipid composition and biophysical properties in microvesiculation on red blood cells but also platelets, immune and nervous cells as well as tumor cells. Although only a few data are available in this respect, most of them appear to converge to the idea that modulation of plasma membrane lipid content, transversal asymmetry and lateral heterogeneity in lipid domains may play a significant role in the vesiculation process. We suggest that lipid domains may represent platforms for inclusion/exclusion of membrane lipids and proteins into MVs and that MVs could originate from distinct domains during physiological processes and disease evolution. Full article
(This article belongs to the Special Issue Cellular Membrane Domains and Organization)
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Open AccessReview Ectopic Neo-Formed Intracellular Membranes in Escherichia coli: A Response to Membrane Protein-Induced Stress Involving Membrane Curvature and Domains
Biomolecules 2018, 8(3), 88; https://doi.org/10.3390/biom8030088
Received: 30 July 2018 / Revised: 31 August 2018 / Accepted: 31 August 2018 / Published: 4 September 2018
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Abstract
Bacterial cytoplasmic membrane stress induced by the overexpression of membrane proteins at high levels can lead to formation of ectopic intracellular membranes. In this review, we report the various observations of such membranes in Escherichia coli, compare their morphological and biochemical characterizations,
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Bacterial cytoplasmic membrane stress induced by the overexpression of membrane proteins at high levels can lead to formation of ectopic intracellular membranes. In this review, we report the various observations of such membranes in Escherichia coli, compare their morphological and biochemical characterizations, and we analyze the underlying molecular processes leading to their formation. Actually, these membranes display either vesicular or tubular structures, are separated or connected to the cytoplasmic membrane, present mono- or polydispersed sizes and shapes, and possess ordered or disordered arrangements. Moreover, their composition differs from that of the cytoplasmic membrane, with high amounts of the overexpressed membrane protein and altered lipid-to-protein ratio and cardiolipin content. These data reveal the importance of membrane domains, based on local specific lipid–protein and protein–protein interactions, with both being crucial for local membrane curvature generation, and they highlight the strong influence of protein structure. Indeed, whether the cylindrically or spherically curvature-active proteins are actively curvogenic or passively curvophilic, the underlying molecular scenarios are different and can be correlated with the morphological features of the neo-formed internal membranes. Delineating these molecular mechanisms is highly desirable for a better understanding of protein–lipid interactions within membrane domains, and for optimization of high-level membrane protein production in E. coli. Full article
(This article belongs to the Special Issue Cellular Membrane Domains and Organization)
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Open AccessReview The Many Faces of Amphipathic Helices
Biomolecules 2018, 8(3), 45; https://doi.org/10.3390/biom8030045
Received: 30 May 2018 / Revised: 2 July 2018 / Accepted: 2 July 2018 / Published: 5 July 2018
Cited by 1 | PDF Full-text (1443 KB) | HTML Full-text | XML Full-text
Abstract
Amphipathic helices (AHs), a secondary feature found in many proteins, are defined by their structure and by the segregation of hydrophobic and polar residues between two faces of the helix. This segregation allows AHs to adsorb at polar–apolar interfaces such as the lipid
[...] Read more.
Amphipathic helices (AHs), a secondary feature found in many proteins, are defined by their structure and by the segregation of hydrophobic and polar residues between two faces of the helix. This segregation allows AHs to adsorb at polar–apolar interfaces such as the lipid surfaces of cellular organelles. Using various examples, we discuss here how variations within this general scheme impart membrane-interacting AHs with different interfacial properties. Among the key parameters are: (i) the size of hydrophobic residues and their density per helical turn; (ii) the nature, the charge, and the distribution of polar residues; and (iii) the length of the AH. Depending on how these parameters are tuned, AHs can deform lipid bilayers, sense membrane curvature, recognize specific lipids, coat lipid droplets, or protect membranes from stress. Via these diverse mechanisms, AHs play important roles in many cellular processes. Full article
(This article belongs to the Special Issue Cellular Membrane Domains and Organization)
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Open AccessReview Anandamide Revisited: How Cholesterol and Ceramides Control Receptor-Dependent and Receptor-Independent Signal Transmission Pathways of a Lipid Neurotransmitter
Biomolecules 2018, 8(2), 31; https://doi.org/10.3390/biom8020031
Received: 3 April 2018 / Revised: 2 May 2018 / Accepted: 16 May 2018 / Published: 22 May 2018
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Abstract
Anandamide is a lipid neurotransmitter derived from arachidonic acid, a polyunsaturated fatty acid. The chemical differences between anandamide and arachidonic acid result in a slightly enhanced solubility in water and absence of an ionisable group for the neurotransmitter compared with the fatty acid.
[...] Read more.
Anandamide is a lipid neurotransmitter derived from arachidonic acid, a polyunsaturated fatty acid. The chemical differences between anandamide and arachidonic acid result in a slightly enhanced solubility in water and absence of an ionisable group for the neurotransmitter compared with the fatty acid. In this review, we first analyze the conformational flexibility of anandamide in aqueous and membrane phases. We next study the interaction of the neurotransmitter with membrane lipids and discuss the molecular basis of the unexpected selectivity of anandamide for cholesterol and ceramide from among other membrane lipids. We show that cholesterol behaves as a binding partner for anandamide, and that following an initial interaction mediated by the establishment of a hydrogen bond, anandamide is attracted towards the membrane interior, where it forms a molecular complex with cholesterol after a functional conformation adaptation to the apolar membrane milieu. The complex is then directed to the anandamide cannabinoid receptor (CB1) which displays a high affinity binding pocket for anandamide. We propose that cholesterol may regulate the entry and exit of anandamide in and out of CB1 by interacting with low affinity cholesterol recognition sites (CARC and CRAC) located in transmembrane helices. The mirror topology of cholesterol binding sites in the seventh transmembrane domain is consistent with the delivery, extraction and flip-flop of anandamide through a coordinated cholesterol-dependent mechanism. The binding of anandamide to ceramide illustrates another key function of membrane lipids which may occur independently of protein receptors. Interestingly, ceramide forms a tight complex with anandamide which blocks the degradation pathway of both lipids and could be exploited for anti-cancer therapies. Full article
(This article belongs to the Special Issue Cellular Membrane Domains and Organization)
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Open AccessReview Brownian Motion at Lipid Membranes: A Comparison of Hydrodynamic Models Describing and Experiments Quantifying Diffusion within Lipid Bilayers
Biomolecules 2018, 8(2), 30; https://doi.org/10.3390/biom8020030
Received: 5 April 2018 / Revised: 7 May 2018 / Accepted: 16 May 2018 / Published: 22 May 2018
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Abstract
The capability of lipid bilayers to exhibit fluid-phase behavior is a fascinating property, which enables, for example, membrane-associated components, such as lipids (domains) and transmembrane proteins, to diffuse within the membrane. These diffusion processes are of paramount importance for cells, as they are
[...] Read more.
The capability of lipid bilayers to exhibit fluid-phase behavior is a fascinating property, which enables, for example, membrane-associated components, such as lipids (domains) and transmembrane proteins, to diffuse within the membrane. These diffusion processes are of paramount importance for cells, as they are for example involved in cell signaling processes or the recycling of membrane components, but also for recently developed analytical approaches, which use differences in the mobility for certain analytical purposes, such as in-membrane purification of membrane proteins or the analysis of multivalent interactions. Here, models describing the Brownian motion of membrane inclusions (lipids, peptides, proteins, and complexes thereof) in model bilayers (giant unilamellar vesicles, black lipid membranes, supported lipid bilayers) are summarized and model predictions are compared with the available experimental data, thereby allowing for evaluating the validity of the introduced models. It will be shown that models describing the diffusion in freestanding (Saffman-Delbrück and Hughes-Pailthorpe-White model) and supported bilayers (the Evans-Sackmann model) are well supported by experiments, though only few experimental studies have been published so far for the latter case, calling for additional tests to reach the same level of experimental confirmation that is currently available for the case of freestanding bilayers. Full article
(This article belongs to the Special Issue Cellular Membrane Domains and Organization)
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Open AccessReview Protein–Phospholipid Interaction Motifs: A Focus on Phosphatidic Acid
Biomolecules 2018, 8(2), 20; https://doi.org/10.3390/biom8020020
Received: 28 February 2018 / Revised: 16 April 2018 / Accepted: 16 April 2018 / Published: 23 April 2018
Cited by 2 | PDF Full-text (804 KB) | HTML Full-text | XML Full-text
Abstract
Cellular membranes are composed of thousands of different lipids usually maintained within a narrow range of concentrations. In addition to their well-known structural and metabolic roles, signaling functions for many lipids have also emerged over the last two decades. The latter largely depend
[...] Read more.
Cellular membranes are composed of thousands of different lipids usually maintained within a narrow range of concentrations. In addition to their well-known structural and metabolic roles, signaling functions for many lipids have also emerged over the last two decades. The latter largely depend on the ability of particular classes of lipids to interact specifically with a great variety of proteins and to regulate their localization and activity. Among these lipids, phosphatidic acid (PA) plays a unique role in a large repertoire of cellular activities, most likely in relation to its unique biophysical properties. However, until recently, only incomplete information was available to model the interaction between PA and its protein partners. The development of new liposome-based assays as well as molecular dynamic simulation are now providing novel information. We will review the different factors that have shown to modulate the capacity of PA to interact with specific domains in target proteins. Full article
(This article belongs to the Special Issue Cellular Membrane Domains and Organization)
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