Submit to Biomolecules Review for Biomolecules Propose a Special Issue

Journal Browser

► Journal Browser

Cellular Membrane Domains and Organization

Special Issue Editors
Special Issue Information
Keywords
Published Papers

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

Deadline for manuscript submissions: closed (30 July 2018) | Viewed by 76680

Share This Special Issue

Special Issue Editors

Dr. Nadège Jamin

E-Mail Website
Guest Editor

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
Interests: protein–lipid interactions; caveolin; structural analysis of membrane proteins

Dr. Stéphane Orlowski

E-Mail Website
Guest Editor

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
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

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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 (11 papers)

Download All Papers

Research

Jump to: Review

14 pages, 624 KiB

Open AccessArticle

Numerical Simulation and FRAP Experiments Show That the Plasma Membrane Binding Protein PH-EFA6 Does Not Exhibit Anomalous Subdiffusion in Cells

by Cyril Favard

Biomolecules 2018, 8(3), 90; https://doi.org/10.3390/biom8030090 - 05 Sep 2018

Cited by 2 | Viewed by 4814

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, 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)

► Show Figures

Graphical abstract

13 pages, 1299 KiB

Open AccessArticle

Determination of the Membrane Environment of CD59 in Living Cells

by Gergő Fülöp, Mario Brameshuber, Andreas M. Arnold, Gerhard J. Schütz and Eva Sevcsik

Biomolecules 2018, 8(2), 28; https://doi.org/10.3390/biom8020028 - 17 May 2018

Cited by 7 | Viewed by 4137

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 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)

► Show Figures

Figure 1

20 pages, 2262 KiB

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

by Muhammad Imran, Odile Sergent, Arnaud Tête, Isabelle Gallais, Martine Chevanne, Dominique Lagadic-Gossmann and Normand Podechard

Biomolecules 2018, 8(2), 26; https://doi.org/10.3390/biom8020026 - 14 May 2018

Cited by 13 | Viewed by 5153

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 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)

► Show Figures

Figure 1

Review

Jump to: Research

25 pages, 2548 KiB

Open AccessEditor’s ChoiceReview

Modeling Membrane Curvature Generation due to Membrane–Protein Interactions

by Haleh Alimohamadi and Padmini Rangamani

Biomolecules 2018, 8(4), 120; https://doi.org/10.3390/biom8040120 - 23 Oct 2018

Cited by 52 | Viewed by 9511

Abstract

To alter and adjust the shape of the plasma membrane, cells harness various mechanisms of curvature generation. Many of these curvature generation mechanisms rely on the interactions between peripheral membrane proteins, integral membrane proteins, and lipids in the bilayer membrane. Mathematical and computational modeling of membrane curvature generation has provided great insights into the physics underlying these processes. However, one of the challenges in modeling these processes is identifying the suitable constitutive relationships that describe the membrane free energy including protein distribution and curvature generation capability. Here, we review some of the commonly used continuum elastic membrane models that have been developed for this purpose and discuss their applications. Finally, we address some fundamental challenges that future theoretical methods need to overcome to push the boundaries of current model applications. Full article

(This article belongs to the Special Issue Cellular Membrane Domains and Organization)

► Show Figures

Figure 1

47 pages, 4584 KiB

Open AccessReview

A Rationale for Mesoscopic Domain Formation in Biomembranes

by Nicolas Destainville, Manoel Manghi and Julie Cornet

Biomolecules 2018, 8(4), 104; https://doi.org/10.3390/biom8040104 - 29 Sep 2018

Cited by 12 | Viewed by 4520

Abstract

Cell plasma membranes display a dramatically rich structural complexity characterized by functional sub-wavelength domains with specific lipid and protein composition. Under favorable experimental conditions, patterned morphologies can also be observed in vitro on model systems such as supported membranes or lipid vesicles. Lipid mixtures separating in liquid-ordered and liquid-disordered phases below a demixing temperature play a pivotal role in this context. Protein-protein and protein-lipid interactions also contribute to membrane shaping by promoting small domains or clusters. Such phase separations displaying characteristic length-scales falling in-between the nanoscopic, molecular scale on the one hand and the macroscopic scale on the other hand, are named mesophases in soft condensed matter physics. In this review, we propose a classification of the diverse mechanisms leading to mesophase separation in biomembranes. We distinguish between mechanisms relying upon equilibrium thermodynamics and those involving out-of-equilibrium mechanisms, notably active membrane recycling. In equilibrium, we especially focus on the many mechanisms that dwell on an up-down symmetry breaking between the upper and lower bilayer leaflets. Symmetry breaking is an ubiquitous mechanism in condensed matter physics at the heart of several important phenomena. In the present case, it can be either spontaneous (domain buckling) or explicit, i.e., due to an external cause (global or local vesicle bending properties). Whenever possible, theoretical predictions and simulation results are confronted to experiments on model systems or living cells, which enables us to identify the most realistic mechanisms from a biological perspective. Full article

(This article belongs to the Special Issue Cellular Membrane Domains and Organization)

► Show Figures

Figure 1

38 pages, 2790 KiB

Open AccessEditor’s ChoiceReview

Plasma Membrane Lipid Domains as Platforms for Vesicle Biogenesis and Shedding?

by Hélène Pollet, Louise Conrard, Anne-Sophie Cloos and Donatienne Tyteca

Biomolecules 2018, 8(3), 94; https://doi.org/10.3390/biom8030094 - 14 Sep 2018

Cited by 91 | Viewed by 9914

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 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)

► Show Figures

Figure 1

23 pages, 880 KiB

Open AccessReview

Ectopic Neo-Formed Intracellular Membranes in Escherichia coli: A Response to Membrane Protein-Induced Stress Involving Membrane Curvature and Domains

by Nadège Jamin, Manuel Garrigos, Christine Jaxel, Annie Frelet-Barrand and Stéphane Orlowski

Biomolecules 2018, 8(3), 88; https://doi.org/10.3390/biom8030088 - 04 Sep 2018

Cited by 11 | Viewed by 4337

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, 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)

► Show Figures

Figure 1

14 pages, 1443 KiB

Open AccessEditor’s ChoiceReview

The Many Faces of Amphipathic Helices

by Manuel Giménez-Andrés, Alenka Čopič and Bruno Antonny

Biomolecules 2018, 8(3), 45; https://doi.org/10.3390/biom8030045 - 05 Jul 2018

Cited by 111 | Viewed by 11473

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 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)

► Show Figures

Graphical abstract

22 pages, 2520 KiB

Open AccessReview

Anandamide Revisited: How Cholesterol and Ceramides Control Receptor-Dependent and Receptor-Independent Signal Transmission Pathways of a Lipid Neurotransmitter

by Coralie Di Scala, Jacques Fantini, Nouara Yahi, Francisco J. Barrantes and Henri Chahinian

Biomolecules 2018, 8(2), 31; https://doi.org/10.3390/biom8020031 - 22 May 2018

Cited by 30 | Viewed by 7043

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. 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)

► Show Figures

Figure 1

13 pages, 3959 KiB

Open AccessReview

Brownian Motion at Lipid Membranes: A Comparison of Hydrodynamic Models Describing and Experiments Quantifying Diffusion within Lipid Bilayers

by Stephan Block

Biomolecules 2018, 8(2), 30; https://doi.org/10.3390/biom8020030 - 22 May 2018

Cited by 20 | Viewed by 5813

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 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)

► Show Figures

Figure 1

9 pages, 804 KiB

Open AccessEditor’s ChoiceReview

Protein–Phospholipid Interaction Motifs: A Focus on Phosphatidic Acid

by Emeline Tanguy, Nawal Kassas and Nicolas Vitale

Biomolecules 2018, 8(2), 20; https://doi.org/10.3390/biom8020020 - 23 Apr 2018

Cited by 52 | Viewed by 8349

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 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)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Cellular Membrane Domains and Organization

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (11 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI