Tag membrane [more than 800 articles]

Abstract

Antimicrobial peptides (AMPs) are not only fast microbe-killing molecules deployed in the host defense of living organisms, but also offer valuable lessons for developing new therapeutic agents. While the mode of action of AMPs is not clearly understood yet, membrane perturbation has been recognized as a crucial step in the microbial killing mechanism of many AMPs. Here, we present a physical basis for the selective membrane-disrupting activity of cationic AMPs. To this end, we present a coarse-grained physical model that approximately ...

Abstract

We report a light microscopy study of interactions between colloidal particles either chemically bound or physisorbed onto flexible giant vesicle fluid membranes. The particles induce pinched shape deformations of the membrane and are driven to negative curvature regions on nonspherical vesicles. The membrane distortions were found to induce interparticle attraction with a range approximately equal to the particle diameter. Multiple particles decorating fluid membranes aggregate into finite-sized two-dimensional close packed aggregates or, unexpectedly, one-dimensional ringlike aggregates. ...

Abstract

The elastic interaction of membrane inclusions provides one of the simplest physical realizations of multibody forces. Here we show how the cross-sectional shape of the inclusion greatly changes the character of the interaction, and illustrates a pattern formation mechanism. The formalism provides a transparent framework for modeling bilayer-inclusion boundary effects on the multibody interaction. ...

Abstract

Membrane proteins can deform the lipid bilayer in which they are embedded. If the bilayer is treated as an elastic medium, then these deformations will generate elastic interactions between the proteins. The interaction between a single pair is repulsive. However, for three or more proteins, we show that there are nonpairwise forces whose magnitude is similar to the pairwise forces. When there are five or more proteins, we show that the nonpairwise forces permit the existence of stable protein aggregates, despite ...

Abstract

Epsin was originally discovered by virtue of its binding to another accessory protein, Eps15. Members of the epsin family play an important role as accessory proteins in clathrin-mediated endocytosis. Epsin isoforms have been described that differ in intracellular site of action and/or in tissue distribution, although all epsins essentially contribute to membrane deformation. Besides inducing membrane curvature, epsin also plays a key function as adaptor protein, coupling various components of the clathrin-assisted uptake and fulfils an important role in selecting and ...

Abstract

The mechanisms by which cytosolic proteins reversibly bind the membrane and induce the curvature for membrane trafficking and remodeling remain elusive. The epsin N-terminal homology (ENTH) domain has potent vesicle tubulation activity despite a lack of intrinsic molecular curvature. EPR revealed that the N-terminal alpha-helix penetrates the phosphatidylinositol 4,5-bisphosphate-containing membrane at a unique oblique angle and concomitantly interacts closely with helices from neighboring molecules in an antiparallel orientation. The quantitative fluorescence microscopy showed that the formation of highly ordered ENTH domain ...

Abstract

The protein epsin is believed to play important roles in clathrin-mediated endocytosis, including generation of the high membrane curvature necessary for vesicle formation. Here we assess the basis for this hypothesis by systematically quantifying the curvature dependence of the area density of epsin N-terminal homology (ENTH) domain on cylindrical membranes of controlled curvature. In cylindrical tethers pulled from micropipet-aspirated giant unilamellar vesicles, repartitioning of membrane-bound ENTH from vesicles onto highly curved membranes was observed by fluorescence microscopy. First-order thermodynamic theory used ...

Abstract

The membrane-bound component F0, which is a major component of the F0F1-ATP synthase, works as a rotary motor and plays a central role in driving the F1 component to transform chemiosmotic energy into ATP synthesis. We conducted molecular dynamics simulations of b2-free F0 in a 1-palmitoyl-2-oleoyl-phosphatidylcholine lipid bilayer for tens of nanoseconds with two different protonation states of the cAsp-61 residue at the interface of the a-c complex in the absence of electric fields and under electric fields of ±0.03 V/nm ...

Abstract

We devise a soft, solvent-free, coarse-grained model for lipid bilayer membranes. The non-bonded interactions take the form of a weighted-density functional which allows us to describe the thermodynamics of self-assembly and packing effects of the coarse-grained beads in terms of a density expansion of the equation of state and the weighting functions that regularize the microscopic bead densities, respectively. Identifying the length and energy scales via the bilayer thickness and the thermal energy scale, kT, the model qualitatively reproduces key characteristics (e.g., bending rigidity, area per lipid molecules, and ...

Abstract

The critical role of membrane proteins in a myriad of biological and physiological functions has spawned numerous investigations over the past several decades with the long-term goal of identifying the molecular origins and energetic forces that stabilize these proteins within the membrane. Parallel structural and thermodynamics studies on several systems have provided significant insight regarding the driving forces governing folding, assembly, insertion, and translocation of membrane proteins. The present review surveys families of membrane-associated proteins including [alpha]-helical and [beta]-barrel structures, viral ...

Abstract

Enveloped viruses infect host cells by fusion of viral and target membranes. This fusion event is triggered by specific glycoproteins in the viral envelope. Fusion glycoproteins belong to either class I, class II or the newly described third class, depending upon their arrangement at the surface of the virion, their tri-dimensional structure and the location within the protein of a short stretch of hydrophobic amino acids called the fusion peptide, which is able to induce the initial lipid destabilization at the ...

Abstract

The shape of enveloped viruses depends critically on an internal protein matrix, yet it remains unclear how the matrix proteins control the geometry of the envelope membrane. We found that matrix proteins purified from Newcastle disease virus adsorb on a phospholipid bilayer and condense into fluidlike domains that cause membrane deformation and budding of spherical vesicles, as seen by fluorescent and electron microscopy. Measurements of the electrical admittance of the membrane resolved the gradual growth and rapid closure of a bud ...

Abstract

Although many membrane additives are known to modulate the activities of membrane proteins via perturbing the properties of lipid membrane, the underlying mechanism is often not precisely understood. In this study, we investigate the impact of asymmetrically incorporating single-tailed lysophosphatidylcholine (LPC) into a membrane bilayer using coarse-grained molecular dynamics simulations. Using a simple computational protocol designed to approximately mimic a micropipette setting, we show that asymmetric incorporation of LPC can lead to significant curvature in a bilayer. Detailed analysis of geometrical ...

Abstract

We discuss the electrostatic contribution to the elastic moduli of a cell or artificial membrane placed in an electrolyte and driven by a DC electric field. The field drives ion currents across the membrane, through specific channels, pumps or natural pores. In steady state, charges accumulate in the Debye layers close to the membrane, modifying the membrane elastic moduli. We first study a model of a membrane of zero thickness, later generalizing this treatment to allow for a finite thickness and ...

Abstract

In the G-protein-coupled receptor (GPCR) rhodopsin, the inactivating ligand 11-cis-retinal is bound in the seven-transmembrane helix (TM) bundle and is cis/trans isomerized by light to form active metarhodopsin II. With metarhodopsin II decay, all-trans-retinal is released, and opsin is reloaded with new 11-cis-retinal. Here we present the crystal structure of ligand-free native opsin from bovine retinal rod cells at 2.9 ångström (Å) resolution. Compared to rhodopsin, opsin shows prominent structural changes in the conserved E(D)RY and NPxxY(x)5,6F regions and in TM5–TM7. ...

Abstract

Rat liver mitochondria were isolated by a combination of differential and Percoll gradient centrifugation, resulting in a highly pure and intact preparation, as assessed by marker enzyme analysis, latency of cytochrome -c oxidase, respiratory control index and electron microscopy. Two different methods were compared for the separation of inner and outer membranes. In the swell-shrink-sonicate procedure glycerol was included resulting in the isolation of one outer membrane and two inner membrane fractions of high purity. Using digitonin a highly selective and ...

Abstract

The (31)P-nuclear magnetic resonance chemical shift of phosphatidic acid in a membrane is sensitive to the lipid head group packing and can report qualitatively on membrane lateral compression near the aqueous interface. We have used high-resolution (31)P-nuclear magnetic resonance to evaluate the lateral compression on each side of asymmetrical lipid vesicles. When monooleoylphosphatidylcholine was added to the external monolayer of sonicated vesicles containing dioleoylphosphatidylcholine and dioleoylphosphatidic acid, the variation of (31)P chemical shift of phosphatidic acid indicated a lateral compression in ...

Abstract

The squid giant axon was used as a model system in which to determine the independent contributions of membrane excitability and diameter changes to threshold parameters and propagation of action potentials in inhomogeneous regions. The membrane excitability of a segment of an axon was altered by changes in the bathing solution, while its effective electrical diameter was increased by the insertion of a low-resistance axial wire. In computer simulations of these experiments, similar alterations were made in the membrane's conductance and ...

Abstract

Recent breakthroughs in the determination of the crystal structures of G protein-coupled receptors (GPCRs) have provided new opportunities for structure-based drug design strategies targeting this protein family. With the aim of evaluating the current status of GPCR structure prediction and ligand docking, a community-wide, blind prediction assessment — GPCR Dock 2008 — was conducted in coordination with the publication of the crystal structure of the human adenosine A2A receptor bound to the ligand ZM241385. Twenty-nine groups submitted 206 structural models before ...

Abstract

The interaction of an arginine (Arg) residue with water in a transmembrane antimicrobial peptide, PG-1, is investigated by two-dimensional heteronuclear correlation (HETCOR), solid-state nuclear magnetic resonance (NMR) spectroscopy. Using 13C and 15N dipolar-edited 1H−15N HETCOR experiments, we unambiguously assigned a water−guanidinium cross-peak that is distinct from intramolecular protein−protein cross-peaks. This water−Arg cross-peak was detected within a short 1H spin diffusion mixing time of 1 ms, indicating that water is in close contact with the membrane-inserted guanidinium. Together with previously observed short ...

Abstract

Inspired by the seminal work of Anfinsen, investigations of the folding of small water-soluble proteins have culminated in detailed insights into how these molecules attain and stabilize their native folds. In contrast, despite their overwhelming importance in biology, progress in understanding the folding and stability of membrane proteins remains relatively limited. Here we use mutational analysis to describe the transition state involved in the reversible folding of the beta-barrel membrane protein PhoPQ-activated gene P (PagP) from a highly disordered state in ...

Abstract

We report a structural study of cholesterol-DPPC (1,2-dipalmitoyl-sn-glycero-3-phophocholine) monolayers using x-ray reflectivity and grazing incidence x-ray diffraction. Reflectivity reveals that the vertical position of cholesterol relative to phospholipids strongly depends on its mole fraction ( χ CHOL ). Moreover, we find that at a broad range of χ CHOL cholesterol and DPPC form alloylike mixed domains of short-range order and the same stoichiometry as that of the film. Based on the data presented, we propose a new model of ...

Abstract

United-atom force fields for molecular dynamics (MD) simulations provide a higher computational efficiency, especially in lipid membrane simulations, with little sacrifice in accuracy, when compared to all-atom force fields. Excellent united-atom lipid models are available, but in combination with depreciated protein force fields. In this work, a united-atom model of the lipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine has been built with standard parameters of the force field GROMOS96 53a6 that reproduces the experimental area per lipid of a lipid bilayer within 3% accuracy to a ...

Abstract

PMID: 20175560 Protein organization on biomembranes and their dynamics are essential for cellular function. It is not clear, however, how protein binding may influence the assembly of underlying lipids or how the membrane structure leads to functional protein organization. Toward this goal, we investigated the effects of annexin a5 binding to biomimetic membranes using fluorescence imaging and correlation spectroscopy. Annexin a5 (anx a5), a peripheral intracellular protein that plays a membrane remodeling role in addition to other functions, binds specifically and ...

Abstract

Membrane tension has been proposed to be important in regulating cell functions such as endocytosis and cell motility. The apparent membrane tension has been calculated from tether forces measured with laser tweezers. Both membrane-cytoskeleton adhesion and membrane tension contribute to the tether force. Separation of the plasma membrane from the cytoskeleton occurs in membrane blebs, which could remove the membrane-cytoskeleton adhesion term. In renal epithelial cells, tether forces are significantly lower on blebs than on membranes that are supported by cytoskeleton. ...

Abstract

To quantitatively predict the mechanical response and mechanically induced remodeling of red blood cells, we developed a multiscale method to correlate distributions of internal stress with overall cell deformation. This method consists of three models at different length scales: in the complete cell level the membrane is modeled as two distinct layers of continuum shells using finite element method (Level III), in which the skeleton-bilayer interactions are depicted as a slide in the lateral (i.e., in-plane) direction (caused by the mobility ...

Abstract

Proton exchange membrane fuel cells have the potential for applications in energy conversion and energy storage, but their development has been impeded by problems with the membrane electrode assembly. Here, we demonstrate that a silicon-based inorganic–organic membrane offers a number of advantages over Nafion—the membrane widely used as a proton exchange membrane in hydrogen fuel cells—including higher proton conductivity, a lack of volumetric size change, and membrane electrode assembly construction capabilities. Key to achieving these advantages is fabricating a silicon membrane ...

Abstract

The nonreceptor tyrosine kinases of the Src family (SFK) are frequently deregulated in human colorectal cancer (CRC), and they have been implicated in tumour growth and metastasis. How SFK are activated in this cancer has not been clearly established. Here, we show that the SFK-dependent invasion is induced by inactivation of the negative regulator C-terminal Src kinase, Csk. While the level of Csk was inconsistent with SFK activity in colon cancer cells, its membrane translocation, needed for efficient regulation of membrane-localized ...

Abstract

Lipophilic ions are widely used as probes for measuring membrane potentials. Since binding of the probes to the membrane interferes with the accurate estimation of the membrane potential, it is necessary to clarify the characteristics of probe binding to membranes. The present paper deals with the binding of lipophilic cations to liposomes. The results can be summarized as follows: (1) The binding of triphenylmethylphosphonium, its homologues and tetraphenylphosphonium to liposomes of dipalmitoylphosphatidylcholine followed the Langmuir adsorption isotherm. (2) Spin-labeled lipophilic cations ...

Abstract

The binding of the lipophilic cation tetraphenylphosphonium to bilayer membranes of 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphocholine was measured in the concentration range of 5 mM to 0.5 M TPP + Cl − . By combining deuterium magnetic resonance with ultraviolet absorption spectroscopy the amount of membrane-bound and free TPP + Cl − could be determined over the whole concentration range measured. After taking into account surface potential effects by means of the Gouy-Chapman theory the binding isotherm could be quantitatively explained by the ...

Abstract

Modernism has rendered ambiguous the role of the wall as a device of definition, confinement and separation and as carrier of symbolic dressing, for it can at one moment outdo itself with mass and at another deny its essence as diaphanous membrane such that it disappears as a physical phenomenon. The wall has been dissolved through technical means. This paper explores via Art, the aesthetics of the wall citing Schmarsow's two 'orders of the wall', an exaggerated function as a limit, ...

Abstract

10.1073/pnas.0913734107 The generation of membrane curvature in intracellular traffic involves many proteins that can curve lipid bilayers. Among these, dynamin-like proteins were shown to deform membranes into tubules, and thus far are the only proteins known to mechanically drive membrane fission. Because dynamin forms a helical coat circling a membrane tubule, its polymerization is thought to be responsible for this membrane deformation. Here we show that the force generated by dynamin polymerization, 18 pN, is sufficient to deform membranes yet can ...

Abstract

10.1073/pnas.0400358101 It has been traditionally difficult to measure the thermodynamic stability of membrane proteins because fully reversible protocols for complete folding these proteins were not available. Knowledge of the thermodynamic stability of membrane proteins is desirable not only from a fundamental theoretical standpoint, but is also of enormous practical interest for the rational design of membrane proteins and for optimizing conditions for their structure determination by crystallography or NMR. Here, we describe the design of a fully reversible system to study ...

Abstract

10.1073/pnas.0914478107 ...

Abstract

This report addresses the following problems associated with the generation of computer models of phospholipid bilayer membranes using molecular dynamics simulations: arbitrary initial structures and short equilibration periods, an Ewald-induced strong coupling of phospholipids, uncertainty regarding which value should be used for surface tension to alleviate the problem of the small size of the membrane, and simultaneous realization of both order parameters and the surface area. We generated a computer model of the liquid-crystalline L-alpha-dimyristoylphosphatidylcholine (DMPC) bilayer, starting from a configuration ...

Abstract

Membrane fluidity plays an important role in cell function and may, in many instances, be adjusted to facilitate specific cellular processes. To understand better the effect that lipid chemistry has on membrane fluidity the inclusion of three different lipids into egg phosphatidylcholine (eggPC) bilayers has been examined; the three lipids are egg phosphatidylethanolamine ((eggPE) made by transphosphatidylation of eggPC in the presence of ethanolamine), lyso-phosphatidylcholine (LPC), and lyso-phosphatidylethanolamine (LPE). The fluidity of the membranes was determined using fluorescence recovery after photobleaching ...

Abstract

Membrane transporters can be major determinants of the pharmacokinetic, safety and efficacy profiles of drugs. This presents several key questions for drug development, including which transporters are clinically important in drug absorption and disposition, and which in vitro methods are suitable for studying drug interactions with these transporters. In addition, what criteria should trigger follow-up clinical studies, and which clinical studies should be conducted if needed. In this article, we provide the recommendations of the International Transporter Consortium on these issues, ...

Abstract

The free energy of transfer of nonpolar solutes from water to lipid bilayers is often dominated by a large negative enthalpy rather than the large positive entropy expected from the hydrophobic effect. This common observation has led to the concept of the "nonclassical" hydrophobic effect and the idea that the "classical" hydrophobic effect may not drive partitioning in many bilayer systems. We show through measurements of the heat capacity changes associated with the partitioning of tryptophan side-chain analogs into lipid bilayers ...

Abstract

We have monitored the organization and dynamics of the hemolytic peptide melittin in membranes containing cholesterol by utilizing the intrinsic fluorescence properties of its functionally important sole tryptophan residue and circular dichroism spectroscopy. The significance of this study is based on the fact that the natural target for melittin is the erythrocyte membrane, which contains high amounts of cholesterol. Our results show that the presence of cholesterol inhibits melittin-induced leakage of lipid vesicles and the extent of inhibition appears to be ...

Abstract

With cellular organelles coming in all shapes and sizes, the principle 'form follows function' is readily discernible through the cytologist's lens. Architecturally, one might ask whether there is feedback in this organization. Does a cell 'know' when it has constructed membrane into the stacks of the Golgi, the cisternae of the mitochondria or the tubules of the endoplasmic reticulum? Proofreading can occur in vivo as both errors in nucleic acids and misfolds in proteins are recognized by the cell. Are there ...

Abstract

We investigate a setup where a cloud of atoms is trapped in an optical lattice potential of a standing wave laser field which is created by retro-reflection on a micro-membrane. The membrane vibrations itself realize a quantum mechanical degree of freedom. We show that the center of mass mode of atoms can be coupled to the vibrational mode of the membrane in free space, and predict a significant sympathetic cooling effect of the membrane when atoms are laser cooled. The controllability of the dissipation rate of the ...

Abstract

A major goal in optomechanics is to observe and control quantum behavior in a system consisting of a mechanical resonator coupled to an optical cavity. Work towards this goal has focused on increasing the strength of the coupling between the mechanical and optical degrees of freedom; however, the form of this coupling is crucial in determining which phenomena can be observed in such a system. Here we demonstrate that avoided crossings in the spectrum of an optical cavity containing a flexible dielectric membrane allow us to realize several ...

Abstract

Vesicles consisting of a bilayer membrane of amphiphilic lipid molecules are remarkably flexible surfaces that show an amazing variety of shapes of different symmetry and topology. Owing to the fluidity of the membrane, shape transitions such as budding can be induced by temperature changes or the action of optical tweezers. Thermally excited shape fluctuations are both strong and slow enough to be visible by video microscopy. Depending on the physical conditions, vesicles adhere to and unbind from each other or a ...

Abstract

As intracellular parasites, viruses rely heavily on the use of numerous cellular machineries for completion of their replication cycle. The recent discovery of the heterogeneous distribution of the various lipids within cell membranes has led to the proposal that sphingolipids and cholesterol tend to segregate in microdomains called membrane rafts. The involvement of membrane rafts in biosynthetic traffic, signal transduction, and endocytosis has suggested that viruses may also take advantage of rafts for completion of some steps of their replication cycle, ...

Abstract

PMID: 1991095 ...

Abstract

Linear peptide antibiotics have been isolated from amphibians, insects and humans and used as templates to design cheaper and more potent analogues for medical applications. Peptides such as cecropins or magainins are ≤40 amino acids in length. Many of them have been prepared by solid-phase peptide synthesis with isotopic labels incorporated at selected sites. Structural analysis by solid-state NMR spectroscopy and other biophysical techniques indicates that these peptide antibiotics strongly interact with lipid membranes. In bilayer environments they exhibit amphipathic α-helical ...

Abstract

Hydrophobic and amphipathic α-helices act as independent functional units in immunogenic or fusogenic polypeptides and constitute important structural building blocks in larger membrane proteins. In order to quantitatively assess the interactions that determine the alignment of membrane-associated α-helices, hydrophobic model peptides containing histidine residues at selected sites were prepared by solid-phase peptide synthesis. CD and solution NMR spectroscopy show that these peptides assume α-helical secondary structures in micellar environments. The chemical shift alterations of the histidine side-chain protons during pH titration ...

Abstract

10.1074/jbc.274.41.29115 The α-helix of the designed amphipathic peptide antibiotic LAH(KKALLALALHHLAHLALHLALALKKA-NH) strongly interacts with phospholipid membranes. The peptide is oriented parallel to the membrane surface under acidic conditions, but transmembrane at physiological pH (Bechinger, B. (1996) 263, 768–775). LAH exhibits antibiotic activities against and ; the peptide does not, however, lyse human red blood cells at bacteriocidal concentrations. The antibiotic activities of LAH are 2 orders of magnitude more pronounced at pH 5 when compared with pH 7.5. Although peptide ...