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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01 Jan 2008
TL;DR: The role of Caveolae/caveolin in cardiac and pulmonary pathophysiology, pharmacologic implications of caveolar localization of signaling molecules, and the possibility that caveolae might serve as a therapeutic target are reviewed.
Abstract: Caveolae, a subset of membrane (lipid) rafts, are flask-like invaginations of the plasma membrane that contain caveolin proteins, which serve as organizing centers for cellular signal transduction. Caveolins (-1, -2, and -3) have cytoplasmic N and C termini, palmitolylation sites, and a scaffolding domain that facilitates interaction and organization of signaling molecules so as to help provide coordinated and efficient signal transduction. Such signaling components include upstream entities (e.g., G protein–coupled receptors (GPCRs), receptor tyrosine kinases, and steroid hormone receptors) and downstream components (e.g., heterotrimeric and low-molecular-weight G proteins, effector enzymes, and ion channels). Diseases associated with aberrant signaling may result in altered localization or expression of signaling proteins in caveolae. Caveolin-knockout mice have numerous abnormalities, some of which may reflect the impact of total body knockout throughout the life span. This review provides a general overview of caveolins and caveolae, signaling molecules that localize to caveolae, the role of caveolae/caveolin in cardiac and pulmonary pathophysiology, pharmacologic implications of caveolar localization of signaling molecules, and the possibility that caveolae might serve as a therapeutic target.
10 citations
TL;DR: The data demonstrated that K562 cells could be attacked and induced apoptosis by lymphocytes, and they would make damages to lymphocytes to escape the surveillance of immune system.
Abstract: Summary
Antitumor immunotherapies, as a prospective approach for local cancer treatment, are attracting increasing interests. To detect the reacting course of immune and tumor cells, we have observed the process of K562 cells (a human erythroleukemic cell line) coculturing with peripheral lymphocytes, and the morphological and ultrastructural alterations of K562 cells and lymphocytes were investigated as well using atomic force microscopy (AFM). AFM morphological imaging revealed that after coculture the apoptosis-like structures such as blebbing, pores, and apoptotic bodies were observed on the K562 cells. Also, the cell-surface roughness decreased significantly, which implied the changes in chemical composition of cell membranes. Moreover, the lymphocytes were damaged to some extent induced by the coculture. The data demonstrated that K562 cells could be attacked and induced apoptosis by lymphocytes, and they would make damages to lymphocytes to escape the surveillance of immune system. SCANNING 35:7-11, 2013. © 2012 Wiley Periodicals, Inc.
10 citations
TL;DR: The main finding is the indication that changes in the cholesterol pool in heart mitochondria induced by swimming exercise are related to an increase in resistance to CaCl2‐induced swelling, probably by remodelling of lipid microdomains, and are not deleterious for mitochondrial bioenergetics.
Abstract: New findings
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What is the central question of this study?
The central question was to establish whether decreased cholesterol content in heart mitochondria caused by prolonged swimming may provoke changes in their bioenergetics and affect resistance to CaCl2-induced mitochondrial swelling
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What is the main finding and its importance?
The main finding is the indication that changes in the cholesterol pool in heart mitochondria induced by swimming exercise are related to an increase in resistance to CaCl2-induced swelling, probably by remodelling of lipid microdomains, and are not deleterious for mitochondrial bioenergetics These findings may contribute to a more complete understanding of the defense system that may prevent mitochondrial degradation during exercise and the protective system of cardiac cell defense in stress conditions
The significance of the reduction of the cholesterol pool in heart mitochondria after exercise is still unknown Recently, published data have suggested that cholesterol may influence the components of mitochondrial contact site and affect mitochondrial swelling Therefore, the aim of this study was to determine whether the decreased cholesterol content in heart mitochondria caused by prolonged swimming may provoke changes in their bioenergetics and result in an increased resistance to calcium chloride-induced mitochondrial swelling Male Wistar rats were divided into a sedentary control group and an exercise group The rats exercised for 3 h, burdened with an additional 3% of their body weight Their hearts were removed immediately after completing the exercise The left ventricle was divided and used for experiments Mitochondrial cholesterol content, membrane fluidity and mitochondrial bioenergetics were measured in the control and exercised rat heart mitochondria To assess whether mitochondrial modifications are linked to disruption of lipid microdomains, methyl-β-cyclodextrin, a well-known lipid microdomain-disrupting agent and cholesterol chelator, was applied to the mitochondria of the control group Cholesterol depletion, increased membrane fluidity and increased resistance to calcium chloride-induced swelling were observed in postexercise heart crude mitochondrial fraction Similar results were achieved in control mitochondria treated with 2% methyl-β-cyclodextrin All of the mitochondrial bioenergetics parameters were similar between the groups Therefore, the disruption of raft-like microdomains appears to be an adaptive change in the rat heart following exercise
10 citations
Cites background from "Dynamics in the plasma membrane: ho..."
...The physical properties of plasma membrane domains can have functional implications for receptor and ion channel activities, signalling, recognition events (Marguet et al. 2006) and for mitochondrial respiration and oxidative phosphorylation....
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TL;DR: A novel formulation comprising a unique amphiphilic molecule, 8-((2-hydroxybenzoyl)amino)octanoate (SHAO), that non-covalently interacts with payloads to increase drug dispersion and diffusion when dosed intratumorally (IT) into solid tumors is described.
Abstract: The recent development of immune-based therapies has improved the outcome for cancer patients; however, adjuvant therapies remain an important line of treatment for several cancer types To maximize efficacy, checkpoint inhibitors are often combined with cytotoxic agents While this approach often leads to increased tumor regression, higher off target toxicity often results in certain patients This report describes a novel formulation comprising a unique amphiphilic molecule, 8-((2-hydroxybenzoyl)amino)octanoate (SHAO), that non-covalently interacts with payloads to increase drug dispersion and diffusion when dosed intratumorally (IT) into solid tumors SHAO is co-formulated with cisplatin and vinblastine (referred to as INT230-6) IT dosing of the novel formulation achieved greater tumor growth inhibition and improved survival in in vivo tumor models compared to the same drugs without enhancer given intravenously or IT INT230-6 treatment increased immune infiltrating cells in injected tumors with 10% to 20% of the animals having complete responses and developing systemic immunity to the cancer INT230-6 was also shown to be synergistic with programmed cell death protein 1 (PD-1) antibodies at improving survival and increasing complete responses INT230-6 induced significant tumor necrosis potentially releasing antigens to induce the systemic immune-based anti-cancer attack This research demonstrates a novel, local treatment approach for cancer that minimizes systemic toxicity while stimulating adaptive immunity
9 citations
TL;DR: In this article, the influence of cyclic lipopeptide surfactin (SU) on the cell plasma membrane (PM) of CHO-K1 cells was investigated and shown that even a low concentration of SU causes significant changes in the membrane fluidity and dynamic molecular organization.
9 citations
References
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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
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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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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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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