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Journal ArticleDOI

Dynamics in the plasma membrane: how to combine fluidity and order

TL;DR: The basic concepts of Brownian diffusion and lipid domain formation in model membranes are summarized and the development of ideas and tools in this field are tracked, outlining key results obtained on the dynamic processes at work in membrane structure and assembly.
Abstract: Cell membranes are fascinating supramolecular aggregates that not only form a barrier between compartments but also harbor many chemical reactions essential to the existence and functioning of a cell. Here, it is proposed to review the molecular dynamics and mosaic organization of the plasma membrane, which are thought to have important functional implications. We will first summarize the basic concepts of Brownian diffusion and lipid domain formation in model membranes and then track the development of ideas and tools in this field, outlining key results obtained on the dynamic processes at work in membrane structure and assembly. We will focus in particular on findings made using fluorescent labeling and imaging procedures to record these dynamic processes. We will also discuss a few examples showing the impact of lateral diffusion on cell signal transduction, and outline some future methodological challenges which must be met before we can answer some of the questions arising in this field of research.

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Citations
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Journal ArticleDOI
TL;DR: In this paper, an amphiphilic Janus nanoparticles (NPs) was designed to target and regulate the lipid rafts via tuning its surface ligand amphiphilicity using coarse-grained molecular dynamics simulations.
Abstract: Due to the differential interactions among lipids and proteins, the plasma membrane can segregate into a series of functional nanoscale membrane domains (“lipid rafts”), which are essential in multiple biological processes such as signaling transduction, protein trafficking and endocytosis. On the other hand, Janus nanoparticles (NPs) have shown great promises in various biomedical applications due to their asymmetric characteristics, which can integrate different surface properties and thus synergetic functions. Hence, in this work, we aim to design an amphiphilic Janus NP to target and regulate the lipid rafts via tuning its surface ligand amphiphilicity using coarse-grained molecular dynamics (MD) simulations. Our µs-scale free coarse-grained MD simulations as well as umbrella sampling free energy calculations indicated that the hydrophobicity of the hydrophobic surface ligands not only determined the lateral membrane partitioning thermodynamics of Janus NPs in phase-separated lipid membranes, but also the difficulty in their insertion into different membrane domains of the lipid membrane. These two factors jointly regulated the lipid raft affinity of Janus NPs. Meanwhile, the hydrophilicity of the hydrophilic surface ligands could affect the insertion ability of Janus NPs. Besides, the ultra-small size could ensure the membrane-bound behavior of Janus NPs without disrupting the overall structure and phase separation kinetics of the lipid membrane. These results may provide valuable insights into the design of functional NPs targeting and controllably regulating the lipid raft.

1 citations

Dissertation
01 Jan 2007
TL;DR: In this article, the authors analyse l'organisation dynamique du recepteur mu opioide humain (hMOR) in relation with ses parametres pharmacologiques and les contraintes de son environnement.
Abstract: La question se pose de l'existence de domaines membranaires permettant de regrouper les differentes proteines necessaires a la transmission du signal par les recepteurs couples aux proteines G (RCPG). Nous avons donc analyse l'organisation dynamique du recepteur mu opioide humain (hMOR) en relation avec ses parametres pharmacologiques et les contraintes de son environnement. Apres avoir verifie la fonctionnalite de T7-EGFP-hMOR dans les SH-SY5Y, sa dynamique laterale a ete etudiee par retour de fluorescence apres photoblanchiment a rayon variable (FRAPrv) et par suivi de particule unique (SPT). A 22°C ces analyses ont revele une double compartimentation des recepteurs : dans des domaines permeables de pres de 1 µm de rayon et dans des domaines de rayon inferieur a 200 nm. De plus, pres d'un tiers des recepteurs presente une diffusion dirigee. Les effets de la variation de temperature, de la destabilisation du cytosquelette d'actine et du blocage de l'interaction proteine G/recepteur ont ete observes afin de mieux comprendre l'origine de ces domaines. Bien que tous les parametres qui y participent ne soient pas encore determines, les resultats indiquent que les proteines G ainsi que le cytosquelette influencent l'organisation membranaire de hMOR. La fixation d'antagonistes ne modifie pas la diffusion du recepteur. Au contraire celle des agonistes entrainent une diminution de la taille des domaines et un ralentissement des recepteurs en lien avec la transmission du signal et l'internalisation. Nos resultats soulignent l'importance de plusieurs parametres sur l'organisation dynamique de hMOR et confortent l'interet de l'utilisation conjointe du FRAP et du SPT.

1 citations

Dissertation
06 Jun 2018
TL;DR: In this article, the authors propose a solution analytique for the fonction d'autocorrelation FCS, based on the STED-FCS technique.
Abstract: Les techniques de super-resolution offrent un nouvel apercu de la description de l'organisation moleculaire dynamique de la membrane plasmique. Parmi ces techniques, la microscopie par depletion d'emission stimulee (stimulated emission depletion, STED) depasse la limite de diffraction optique et atteint une resolution de quelques dizaines de nanometres. Il est une technique polyvalente qui peut etre combinee avec d'autres techniques telles que la spectroscopie par correlation de fluorescence (fluorescence correlation spectroscopy, FCS), fournissant des resolutions spatiales et temporelles elevees pour explorer les processus dynamiques qui se produisent dans les cellules vivantes. Ce projet de doctorat vise a mettre en œuvre un microscope STED, puis a combiner ce module STED avec la technique FCS pour les applications biologiques. Des etudes theoriques du STED et de la technique combinant STED et FCS ont permis dans les aspects spatio-temporels. Une solution analytique pour la fonction d'autocorrelation FCS a ete derivee dans l'etat de depletion STED incomplet. et un nouveau modele d'ajustement FCS a ete propose. La methode de variation du volume d’observation FCS (spot variation FCS, svFCS) a demontre sa capacite a identifier la presence de nanodomaines limitant la diffusion laterale des molecules dans la membrane plasmique. L’approche STED-FCS permet d’etendre l’application de la svFCS a l'echelle nanometrique afin d’evaluer la persistance plus ou moins importante de tels nanodomaines. Dans ce contexte, des simulations preliminaires de Monte Carlo ont ete realisees figurant des molecules diffusant en presence d'auto-assemblage/desassemblage dynamique des nanodomaines.

1 citations


Cites background or methods from "Dynamics in the plasma membrane: ho..."

  • ...This calibration can be done by either scanning fluorescent nanoparticles or by deciphering the transit time of freely diffusing molecules using FCS measurement [12,27]....

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  • ...Due to the nano-scale size and the highly dynamic nature of these domains, the study of these heterogeneities in live cell membrane requires observation techniques with both high spatial and temporal resolutions [27, 28]....

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Journal Article
TL;DR: Lipid rafts are chemically distinct compartments of the plasma membrane that are a prerequisite for vital cellular functions particularly for signalling and trafficking and some of the raft associated molecules are useful immunohistochemical markers in routine histopathology.
Abstract: Lipid rafts are chemically distinct compartments of the plasma membrane. Their integrity is a prerequisite for vital cellular functions particularly for signalling and trafficking. Their perturbation is associated with development of a broad spectrum of diseases. Lipid rafts are also important for therapeutic effects of some drugs. Moreover, some of the raft associated molecules are useful immunohistochemical markers in routine histopathology.

1 citations

Journal ArticleDOI
TL;DR: It is concluded that UDCA-LPE executes its action by iPLA2β removal from DRM-PM and consequent dissolution of the raft lipid platform.
Abstract: The bile acid-phospholipid conjugate ursodeoxycholyl-lysophosphatidylethanolamide (UDCA-LPE) was shown to have anti-inflammatory, antisteatotic, and antifibrotic properties, rendering it as a drug targeting non-alcoholic steatohepatitis (NASH). On a molecular level, it disrupted the heterotetrameric fatty acid uptake complex localized in detergent-resistant membrane domains of the plasma membrane (DRM-PM). However, its mode of action was unclear. Methodologically, UDCA-LPE was incubated with the liver tumor cell line HepG2 as well as their isolated DRM-PM and all other cellular membranes (non-DRM). The membrane cholesterol and phospholipids were quantified as well as the DRM-PM protein composition by Western blotting. The results show a loss of DRM-PM by UDCA-LPE (50 µM) with a 63.13 ± 7.14% reduction of phospholipids and an 81.94 ± 8.30% reduction of cholesterol in relation to mg total protein. The ratio of phospholipids to cholesterol changed from 2:1 to 4:1, resembling those of non-DRM fractions. Among the members of the fatty acid uptake complex, the calcium-independent membrane phospholipase A2 (iPLA2β) abandoned DRM-PM most rapidly. As a consequence, the other members of this transport system disappeared as well as the DRM-PM anchored fibrosis regulating proteins integrin β-1 and lysophospholipid receptor 1 (LPAR-1). It is concluded that UDCA-LPE executes its action by iPLA2β removal from DRM-PM and consequent dissolution of the raft lipid platform.

1 citations

References
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Journal ArticleDOI
18 Feb 1972-Science
TL;DR: Results strongly indicate that the bivalent antibodies produce an aggregation of the surface immunoglobulin molecules in the plane of the membrane, which can occur only if the immunoglOBulin molecules are free to diffuse in the membrane.
Abstract: A fluid mosaic model is presented for the gross organization and structure of the proteins and lipids of biological membranes. The model is consistent with the restrictions imposed by thermodynamics. In this model, the proteins that are integral to the membrane are a heterogeneous set of globular molecules, each arranged in an amphipathic structure, that is, with the ionic and highly polar groups protruding from the membrane into the aqueous phase, and the nonpolar groups largely buried in the hydrophobic interior of the membrane. These globular molecules are partially embedded in a matrix of phospholipid. The bulk of the phospholipid is organized as a discontinuous, fluid bilayer, although a small fraction of the lipid may interact specifically with the membrane proteins. The fluid mosaic structure is therefore formally analogous to a two-dimensional oriented solution of integral proteins (or lipoproteins) in the viscous phospholipid bilayer solvent. Recent experiments with a wide variety of techniqes and several different membrane systems are described, all of which abet consistent with, and add much detail to, the fluid mosaic model. It therefore seems appropriate to suggest possible mechanisms for various membrane functions and membrane-mediated phenomena in the light of the model. As examples, experimentally testable mechanisms are suggested for cell surface changes in malignant transformation, and for cooperative effects exhibited in the interactions of membranes with some specific ligands. Note added in proof: Since this article was written, we have obtained electron microscopic evidence (69) that the concanavalin A binding sites on the membranes of SV40 virus-transformed mouse fibroblasts (3T3 cells) are more clustered than the sites on the membranes of normal cells, as predicted by the hypothesis represented in Fig. 7B. T-here has also appeared a study by Taylor et al. (70) showing the remarkable effects produced on lymphocytes by the addition of antibodies directed to their surface immunoglobulin molecules. The antibodies induce a redistribution and pinocytosis of these surface immunoglobulins, so that within about 30 minutes at 37 degrees C the surface immunoglobulins are completely swept out of the membrane. These effects do not occur, however, if the bivalent antibodies are replaced by their univalent Fab fragments or if the antibody experiments are carried out at 0 degrees C instead of 37 degrees C. These and related results strongly indicate that the bivalent antibodies produce an aggregation of the surface immunoglobulin molecules in the plane of the membrane, which can occur only if the immunoglobulin molecules are free to diffuse in the membrane. This aggregation then appears to trigger off the pinocytosis of the membrane components by some unknown mechanism. Such membrane transformations may be of crucial importance in the induction of an antibody response to an antigen, as well as iv other processes of cell differentiation.

7,790 citations

Journal ArticleDOI
28 Jan 2005-Science
TL;DR: The new generations of qdots have far-reaching potential for the study of intracellular processes at the single-molecule level, high-resolution cellular imaging, long-term in vivo observation of cell trafficking, tumor targeting, and diagnostics.
Abstract: Research on fluorescent semiconductor nanocrystals (also known as quantum dots or qdots) has evolved over the past two decades from electronic materials science to biological applications. We review current approaches to the synthesis, solubilization, and functionalization of qdots and their applications to cell and animal biology. Recent examples of their experimental use include the observation of diffusion of individual glycine receptors in living neurons and the identification of lymph nodes in live animals by near-infrared emission during surgery. The new generations of qdots have farreaching potential for the study of intracellular processes at the single-molecule level, high-resolution cellular imaging, long-term in vivo observation of cell trafficking, tumor targeting, and diagnostics.

7,499 citations


"Dynamics in the plasma membrane: ho..." refers background in this paper

  • ...The use of fluorescent quantum dots is emerging as a promising alternative to classical fluorescent tags (GFPs and organic fluorophores) (Michalet et al, 2005)....

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  • ...…quantum yields, large molar extinction coefficients, size-dependent tunable emission and high photostability) make them appeal- &2006 European Molecular Biology Organization The EMBO Journal VOL 25 | NO 15 | 2006 3449 ing candidate tags for use with SDT (Dahan et al, 2003; Michalet et al, 2005)....

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Journal ArticleDOI
TL;DR: This review looks at current methods for preparing QD bioconjugates as well as presenting an overview of applications, and concludes that the potential of QDs in biology has just begun to be realized and new avenues will arise as the ability to manipulate these materials improves.
Abstract: One of the fastest moving and most exciting interfaces of nanotechnology is the use of quantum dots (QDs) in biology. The unique optical properties of QDs make them appealing as in vivo and in vitro fluorophores in a variety of biological investigations, in which traditional fluorescent labels based on organic molecules fall short of providing long-term stability and simultaneous detection of multiple signals. The ability to make QDs water soluble and target them to specific biomolecules has led to promising applications in cellular labelling, deep-tissue imaging, assay labelling and as efficient fluorescence resonance energy transfer donors. Despite recent progress, much work still needs to be done to achieve reproducible and robust surface functionalization and develop flexible bioconjugation techniques. In this review, we look at current methods for preparing QD bioconjugates as well as presenting an overview of applications. The potential of QDs in biology has just begun to be realized and new avenues will arise as our ability to manipulate these materials improves.

5,875 citations


"Dynamics in the plasma membrane: ho..." refers background in this paper

  • ...However, there is still a need to improve the functionalization of QD surfaces, the flexibility for bioconjugations and single irreversible molecular associations between individually tracked molecules (Medintz et al, 2005)....

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Book
01 Jan 1983
TL;DR: This book is a lucid, straightforward introduction to the concepts and techniques of statistical physics that students of biology, biochemistry, and biophysics must know.
Abstract: This book is a lucid, straightforward introduction to the concepts and techniques of statistical physics that students of biology, biochemistry, and biophysics must know. It provides a sound basis for understanding random motions of molecules, subcellular particles, or cells, or of processes that depend on such motion or are markedly affected by it. Readers do not need to understand thermodynamics in order to acquire a knowledge of the physics involved in diffusion, sedimentation, electrophoresis, chromatography, and cell motility--subjects that become lively and immediate when the author discusses them in terms of random walks of individual particles.

3,041 citations


"Dynamics in the plasma membrane: ho..." refers background in this paper

  • ...Brownian motion is a principle that applies to all biological systems (Berg, 1983): as the result of thermal agitation processes, molecules are constantly on the move, colliding with each other and bouncing back and forth (Figure 1)....

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  • ...…plasma membrane dynamics Brownian motion, diffusion and membrane organization Brownian motion is a principle that applies to all biological systems (Berg, 1983): as the result of thermal agitation processes, molecules are constantly on the move, colliding with each other and bouncing back and…...

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Journal ArticleDOI
TL;DR: A unified characterization of the best available FPs provides a useful guide in narrowing down the options for biological imaging tools.
Abstract: The recent explosion in the diversity of available fluorescent proteins (FPs) promises a wide variety of new tools for biological imaging. With no unified standard for assessing these tools, however, a researcher is faced with difficult questions. Which FPs are best for general use? Which are the brightest? What additional factors determine which are best for a given experiment? Although in many cases, a trial-and-error approach may still be necessary in determining the answers to these questions, a unified characterization of the best available FPs provides a useful guide in narrowing down the options.

2,933 citations


"Dynamics in the plasma membrane: ho..." refers background in this paper

  • ...As the cDNA encoding the GFP was characterized, a wide variety of monomeric fluorescent proteins have provided attractive potential candidates for monitoring dynamic processes in which different molecular species are simultaneously involved (for a review, see Shaner et al, 2005)....

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