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1293 records returned

High-chloride concentrations abolish the binding of adenine nucleotides in the mitochondrial ADP/ATP carrier family.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The ADP/ATP carrier (AAC) is a very effective membrane protein that mediates the exchange of ADP and ATP across the mitochondrial membrane. In vivo transport measurements on the AAC overexpressed in Escherichia coli demonstrate that this process can be severely inhibited by high-chloride concentrations. Molecular-dynamics simulations reveal a strong modification of the topology of the local electric field related to the number of chloride ions inside the cavity. Halide ions are shown to shield the positive charges lining the internal cavity of the carrier by accurate targeting of key basic residues. These specific amin...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Krammer EM, Ravaud S, Dehez F, Frelet-Barrand A, Pebay-Peyroula E, Chipot C Tags: Biophys J Source Type: journals

Effectiveness of hair bundle motility as the cochlear amplifier.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The effectiveness of hair bundle motility in mammalian and avian ears is studied by examining energy balance for a small sinusoidal displacement of the hair bundle. The condition that the energy generated by a hair bundle must be greater than energy loss due to the shear in the subtectorial gap per hair bundle leads to a limiting frequency that can be supported by hair-bundle motility. Limiting frequencies are obtained for two motile mechanisms for fast adaptation, the channel re-closure model and a model that assumes that fast adaptation is an interplay between gating of the channel and the myosin motor. The limiting ...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Sul B, Iwasa KH Tags: Biophys J Source Type: journals

Organization of ryanodine receptors, transverse tubules, and sodium-calcium exchanger in rat myocytes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Confocal and total internal reflection fluorescence imaging was used to examine the distribution of caveolin-3, sodium-calcium exchange (NCX) and ryanodine receptors (RyRs) in rat ventricular myocytes. Transverse and longitudinal optical sectioning shows that NCX is distributed widely along the transverse and longitudinal tubular system (t-system). The NCX labeling consisted of both punctate and distributed components, which partially colocalize with RyRs (27%). Surface membrane labeling showed a similar pattern but the fraction of RyR clusters containing NCX label was decreased and no nonpunctate labeling was observed...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Jayasinghe ID, Cannell MB, Soeller C Tags: Biophys J Source Type: journals

A model of Na+/H+ exchanger and its central role in regulation of pH and Na+ in cardiac myocytes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A new kinetic model of the Na(+)/H(+) exchanger (NHE) was developed by fitting a variety of major experimental findings, such as ion-dependencies, forward/reverse mode, and the turnover rate. The role of NHE in ion homeostasis was examined by implementing the NHE model in a minimum cell model including intracellular pH buffer, Na(+)/K(+) pump, background H(+), and Na(+) fluxes. This minimum cell model was validated by reconstructing recovery of pH(i) from acidification, accompanying transient increase in [Na(+)](i) due to NHE activity. Based on this cell model, steady-state relationships among pH(i), [Na(+)](I), and [C...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Cha CY, Oka C, Earm YE, Wakabayashi S, Noma A Tags: Biophys J Source Type: journals

Anthropomorphizing the mouse cardiac action potential via a novel dynamic clamp method.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We present a hybrid computational-experimental technique, the cell-type transforming clamp, which is designed to overcome such differences by using a calculated compensatory current to convert the macroscopic electrical behavior of an isolated cell into that of a different cell type. We demonstrate the technique's utility by evaluating drug arrhythmogenicity in murine cardiomyocytes that are transformed to behave like human myocytes. Whereas we use the cell-type transforming clamp in this work to convert between mouse and human electrodynamics, the technique could be adapted to convert between the action potential morpholo...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Ahrens-Nicklas RC, Christini DJ Tags: Biophys J Source Type: journals

The role of sarcolipin and ATP in the transport of phosphate ion into the sarcoplasmic reticulum.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, SLN acts as an ATP-induced phosphate carrier exhibiting a behavior quite similar to that of the unidentified P(i) transporter described previously. No ion-channel activity is exhibited by the T18A mutant of SLN. PMID: 19917222 [PubMed - in process] (Source: Biophysical Journal)
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Becucci L, Guidelli R, Karim CB, Thomas DD, Veglia G Tags: Biophys J Source Type: journals

Phase separation in binary mixtures of bipolar and monopolar lipid dispersions revealed by 2H NMR spectroscopy, small angle x-ray scattering, and molecular theory.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Binary mixtures of C(20)BAS and POPC membranes were studied by solid-state (2)H NMR spectroscopy and small angle x-ray scattering (SAXS) over a wide range of concentrations and at different temperatures. Three specifically deuterated C(20)BAS derivatives--[1',1',20',20'-(2)H(4)]C(20)BAS, [2',2',19',19'-(2)H(4)]C(20)BAS, and [10',11'-(2)H(2)]C(20)BAS--combined with protiated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), as well as membranes containing POPC-d(31) and fully protiated bolalipid, were used in NMR experiments to obtain structural information for the mixtures. The (2)H NMR spectra of [10',11'-(2)H(...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Brownholland DP, Longo GS, Struts AV, Justice MJ, Szleifer I, Petrache HI, Brown MF, Thompson DH Tags: Biophys J Source Type: journals

Wave propagation in lipid monolayers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Sound waves are excited on lipid monolayers using a set of planar electrodes aligned in parallel with the excitable medium. By measuring the frequency-dependent change in the lateral pressure, we are able to extract the sound velocity for the entire monolayer phase diagram. We demonstrate that this velocity can also be directly derived from the lipid monolayer compressibility, and consequently displays a minimum in the phase transition regime. This minimum decreases from v(0) = 170 m/s for one-component lipid monolayers down to v(m) = 50 m/s for lipid mixtures. No significant attenuation can be detected confirming an a...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Griesbauer J, Wixforth A, Schneider MF Tags: Biophys J Source Type: journals

Coexistence of immiscible mixtures of palmitoylsphingomyelin and palmitoylceramide in monolayers and bilayers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A combination of lipid monolayer- and bilayer-based model systems has been applied to explore in detail the interactions between and organization of palmitoylsphingomyelin (pSM) and the related lipid palmitoylceramide (pCer). Langmuir balance measurements of the binary mixture reveal favorable interactions between the lipid molecules. A thermodynamically stable point is observed in the range approximately 30-40 mol % pCer. The pSM monolayer undergoes hyperpolarization and condensation with small concentrations of pCer, narrowing the liquid-expanded (LE) to liquid-condensed (LC) pSM main phase transition by inducing int...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Busto JV, Fanani ML, De Tullio L, Sot J, Maggio B, Goñi FM, Alonso A Tags: Biophys J Source Type: journals

Membrane-bending mechanism of amphiphysin N-BAR domains.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
BAR domains are highly conserved protein domains participating in a diversity of cellular processes that involve membrane remodeling. The mechanisms underlying such remodeling are debated. For the relatively well-studied case of amphiphysin N-BAR domain, one suggested mechanism involves scaffolding, i.e., binding of a negatively charged membrane to the protein's positively charged curved surface. An alternative mechanism suggests that insertion of the protein's N-terminal amphipathic segments (N-helices H0) into the membrane leads to bending. Here, we address the issue through all-atom and coarse-grained simulations of...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Arkhipov A, Yin Y, Schulten K Tags: Biophys J Source Type: journals

Pulmonary surfactant protein SP-C counteracts the deleterious effects of cholesterol on the activity of surfactant films under physiologically relevant compression-expansion dynamics.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we analyzed the effect of SP-C on the thermodynamic properties of phospholipid membranes containing cholesterol, and the ability of lipid/protein complexes containing cholesterol to form and respread interfacial films capable of producing very low surface tensions upon repetitive compression-expansion cycling. SP-C modulates the effect of cholesterol to reduce the enthalpy associated with the gel-to-liquid-crystalline melting transition in dipalmitoylphosphatidylcholine (DPPC) bilayers, as analyzed by differential scanning calorimetry. The presence of SP-C affects more subtly the effects of cholesterol on th...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Gómez-Gil L, Schürch D, Goormaghtigh E, Pérez-Gil J Tags: Biophys J Source Type: journals

Membrane binding by the endophilin N-BAR domain.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The structure of the endophilin N-terminal amphipathic helix Bin/Amphiphysin/Rvs-homology (N-BAR) domain is unique because of an additional insert helix under the arch of the N-BAR dimer. The structure of this additional helix has not been fully resolved in crystallographic studies, and thus presents a challenge to molecular-level analysis. Large-scale molecular-dynamics simulations were therefore employed to investigate the interaction of a single endophilin N-BAR with a lipid bilayer. Various possible configurations of the additional insert helix under the top of the arch of the endophilin N-BAR were modeled to exami...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Cui H, Ayton GS, Voth GA Tags: Biophys J Source Type: journals

Undulation contributions to the area compressibility in lipid bilayer simulations.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
It is here shown that there is a considerable system size-dependence in the area compressibility calculated from area fluctuations in lipid bilayers. This is caused by the contributions to the area fluctuations from undulations. This is also the case in experiments. At present, such a contribution, in most cases, is subtracted from the experimental values to obtain a true area compressibility. This should also be done with the simulation values. Here, this is done by extrapolating area compressibility versus system size, down to very small (zero) system size, where undulations no longer exist. The area compressibility ...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Waheed Q, Edholm O Tags: Biophys J Source Type: journals

Mechanosensitive closed-closed transitions in large membrane proteins: osmoprotection and tension damping.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Multiconformation membrane proteins are mechanosensitive (MS) if their conformations displace different bilayer areas. Might MS closed-closed transitions serve as tension buffers, that is, as membrane "spandex"? While bilayer expansion is effectively instantaneous, transitions of bilayer-embedded MS proteins are stochastic (thermally activated) so spandex kinetics would be critical. Here we model generic two-state (contracted/expanded) stochastic spandexes inspired by known bacterial osmovalves (MscL, MscS) then suggest experimental approaches to test for spandex-like behaviors in these proteins. Modeling shows: 1), sp...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Boucher PA, Morris CE, Joós B Tags: Biophys J Source Type: journals

Controlling the orientation and synaptic differentiation of myotubes with micropatterned substrates.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Micropatterned poly(dimethylsiloxane) substrates fabricated by soft lithography led to large-scale orientation of myoblasts in culture, thereby controlling the orientation of the myotubes they formed. Fusion occurred on many chemically identical surfaces in which varying structures were arranged in square or hexagonal lattices, but only a subset of patterned surfaces yielded aligned myotubes. Remarkably, on some substrates, large populations of myotubes oriented at a reproducible acute angle to the lattice of patterned features. A simple geometrical model predicts the angle and extent of orientation based on maximizing...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Gingras J, Rioux RM, Cuvelier D, Geisse NA, Lichtman JW, Whitesides GM, Mahadevan L, Sanes JR Tags: Biophys J Source Type: journals

Binding kinetics of bisintercalator Triostin a with optical tweezers force mechanics.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The binding kinetics of the intercalative binding of Triostin A to lambda-DNA was investigated by measuring the force extension response of the DNA-ligand complexes with an optical tweezers system. These force response curves, containing the information about different binding properties, were analyzed based on a recent method (put forth by another research group) for monointercalators that was extended to bisintercalators. Our binding analysis reveals an exponential dependence of the association constant on the applied external force as well as a decreasing binding site size. In general, our results are in agreement w...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Kleimann C, Sischka A, Spiering A, Tönsing K, Sewald N, Diederichsen U, Anselmetti D Tags: Biophys J Source Type: journals

Coarse-Grained Brownian Dynamics Simulations of the 10-23 DNAzyme.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Deoxyribozymes (DNAzymes) are single-stranded DNA that catalyze nucleic acid biochemistry. Although a number of DNAzymes have been discovered by in vitro selection, the relationship between their tertiary structure and function remains unknown. We focus here on the well-studied 10-23 DNAzyme, which cleaves mRNA with a catalytic efficiency approaching that of RNase A. Using coarse-grained Brownian dynamics simulations, we find that the DNAzyme bends its substrate away from the cleavage point, exposing the reactive site and buckling the DNAzyme catalytic core. This hypothesized transition state provides microscopic insig...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Kenward M, Dorfman KD Tags: Biophys J Source Type: journals

Configuration of PKCalpha-C2 domain bound to mixed SOPC/SOPS lipid monolayers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
X-ray reflectivity measurements are used to determine the configuration of the C2 domain of protein kinase Calpha (PKCalpha-C2) bound to a lipid monolayer of a 7:3 mixture of 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine and 1-stearoyl-2-oleoyl-sn-glycero-3-phosphoserine supported on a buffered aqueous solution. The reflectivity is analyzed in terms of the known crystallographic structure of PKCalpha-C2 and a slab model representation of the lipid layer. The configuration of lipid-bound PKCalpha-C2 is described by two angles that define its orientation, theta = 35 degrees +/- 10 degrees and phi =210 degrees +/- 30 de...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Chen CH, Málková S, Pingali SV, Long F, Garde S, Cho W, Schlossman ML Tags: Biophys J Source Type: journals

A second look at mini-protein stability: analysis of FSD-1 using circular dichroism, differential scanning calorimetry, and simulations.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mini-proteins that contain <50 amino acids often serve as model systems for studying protein folding because their small size makes long timescale simulations possible. However, not all mini-proteins are created equal. The stability and structure of FSD-1, a 28-residue mini-protein that adopted the betabetaalpha zinc-finger motif independent of zinc binding, was investigated using circular dichroism, differential scanning calorimetry, and replica-exchange molecular dynamics. The broad melting transition of FSD-1, similar to that of a helix-to-coil transition, was observed by using circular dichroism, differential sc...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Feng JA, Kao J, Marshall GR Tags: Biophys J Source Type: journals

Thermal-induced dissociation and unfolding of homodimeric DsbC revealed by temperature-jump time-resolved infrared spectra.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The thermal stability of DsbC, a homodimeric protein disulfide isomerase in prokaryotic periplasm, has been studied by using temperature-dependent Fourier transformation infrared and time-resolved infrared spectroscopy coupled with temperature-jump initiation. The infrared absorbance thermal titration curves for thermal-induced unfolding of DsbC in D(2)O exhibit a three-state transition with the first transition midpoint temperature at 37.1 +/- 1.1 degrees C corresponding to dissociation, and the second at >74.5 degrees C corresponding to global unfolding and aggregation. The dissociation midpoint temperature of Dsb...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Li H, Ke H, Ren G, Qiu X, Weng YX, Wang CC Tags: Biophys J Source Type: journals

Kinetics of the Multistep Rupture of Fibrin 'A-a' Polymerization Interactions Measured Using Atomic Force Microscopy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Fibrin, the structural scaffold of blood clots, spontaneously polymerizes through the formation of 'A-a' knob-hole bonds. When subjected to external force, the dissociation of this bond is accompanied by two to four abrupt changes in molecular dimension observable as rupture events in a force curve. Herein, the configuration, molecular extension, and kinetic parameters of each rupture event are examined. The increases in contour length indicate that the D region of fibrinogen can lengthen by approximately 50% of the length of a fibrin monomer before rupture of the 'A-a' interaction. The dependence of the dissociation r...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Averett LE, Schoenfisch MH, Akhremitchev BB, Gorkun OV Tags: Biophys J Source Type: journals

Tetracycline-tet repressor binding specificity: insights from experiments and simulations.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Tetracycline (Tc) antibiotics have been put to new uses in the construction of artificial gene regulation systems, where they bind to the Tet repressor protein (TetR) and modulate its affinity for DNA. Many Tc variants have been produced, both to overcome bacterial resistance and to achieve a broad range of binding strengths. To better understand TetR-Tc binding, we investigate a library of 16 tetracyclines, using fluorescence experiments and molecular dynamics free energy simulations (MDFE). The relative TetR binding free energies are computed by reversibly transforming one Tc variant into another during the simulatio...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Aleksandrov A, Schuldt L, Hinrichs W, Simonson T Tags: Biophys J Source Type: journals

A self-consistent description of the conformational behavior of chemically denatured proteins from NMR and small angle scattering.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Characterization of the conformational properties of unfolded proteins is essential for understanding the mechanisms of protein folding and misfolding. This information is also fundamental to determining the relationship between flexibility and function in the highly diverse families of intrinsically disordered proteins. Here we present a self-consistent model of conformational sampling of chemically denatured proteins in agreement with experimental data reporting on long-range distance distributions in unfolded proteins using small-angle x-ray scattering and nuclear magnetic resonance pulse-field gradient-based measur...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Bernadó P, Blackledge M Tags: Biophys J Source Type: journals

Binding hot spots and amantadine orientation in the influenza a virus m2 proton channel.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Structures of truncated versions of the influenza A virus M2 proton channel have been determined recently by x-ray crystallography in the open conformation of the channel, and by NMR in the closed state. The structures differ in the position of the bound inhibitors. The x-ray structure shows a single amantadine molecule in the middle of the channel, whereas in the NMR structure four drug molecules bind at the channel's outer surface. To study this controversy we applied computational solvent mapping, a technique developed for the identification of the most druggable binding hot spots of proteins. The method moves molec...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Chuang GY, Kozakov D, Brenke R, Beglov D, Guarnieri F, Vajda S Tags: Biophys J Source Type: journals

Quantitative imaging of molecular order in lipid membranes using two-photon fluorescence polarimetry.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We present a polarimetric two-photon microscopy technique to quantitatively image the local static molecular orientational behavior in lipid and cell membranes. This approach, based on a tunable excitation polarization state complemented by a polarized readout, is easily implementable and does not require hypotheses on the molecular angular distribution such as its mean orientation, which is a main limitation in traditional fluorescence anisotropy measurements. The method is applied to the investigation of the molecular angular distribution in giant unilamellar vesicles formed by liquid-ordered and liquid-disordered micro-...
Source: Biophysical Journal - November 18, 2009 Category: Physics Authors: Gasecka A, Han TJ, Favard C, Cho BR, Brasselet S Tags: Biophys J Source Type: journals

Direct and model free calculation of force-dependent dissociation rates from force spectroscopic data.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We present a simple and model free approach to extract the force-dependent dissociation rates directly from the force curve data. Simulations show that the dissociation rates at any force are given directly by the ratio of the number of detected rupture events to the time this force was acting on the bond. To calculate these total times of acting forces, all force curve data points of all curves measured are taken into account, which significantly increases the amount of information which is considered for data analysis compared to other methods. Moreover, by providing force-dependent dissociation rates this method allows ...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Oberbarnscheidt L, Janissen R, Oesterhelt F Tags: Biophys J Source Type: journals

Long fluorescence lifetime molecular probes based on near infrared pyrrolopyrrole cyanine fluorophores for in vivo imaging.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we demonstrate that a new class of NIR fluorescent dyes, pyrrolopyrrole cyanine dyes, have exceptionally long FLTs ranging from 3 to 4 ns, both in vitro (dimethyl sulfoxide and albumin/water solutions) and in vivo (mice). These results provide a new window for imaging molecular processes, rejecting backscattered light and autofluorescence, and multiplexing imaging information with conventional NIR fluorescent dyes that absorb and emit light at similar wavelengths. PMID: 19883579 [PubMed - in process] (Source: Biophysical Journal)
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Berezin MY, Akers WJ, Guo K, Fischer GM, Daltrozzo E, Zumbusch A, Achilefu S Tags: Biophys J Source Type: journals

Transport theory for HIV diffusion through in vivo distributions of topical microbicide gels.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study suggests that gel distribution in layers of thickness >100 microm and fractional area coated >0.8 is critical in determining the ability of the gel to serve as a barrier to HIV diffusion. PMID: 19883580 [PubMed - in process] (Source: Biophysical Journal)
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Lai BE, Henderson MH, Peters JJ, Walmer DK, Katz DF Tags: Biophys J Source Type: journals

A cAMP signaling model explains the benefit of maintaining two forms of phosphodiesterase in Dictyostelium.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Starving Dictyostelium cells respond chemotactically to cell-generated waves of cyclic adenosine -3',5'- monophosphate (cAMP) that guide cell aggregation toward a signaling center. In this process, a large number of cells are recruited, resulting in the formation of aggregation territories that are essential for fruiting body formation. The enzyme PdsA phosphodiesterase (PDE), a crucial component of the signaling system, breaks down the external cAMP and can be either membrane-bound or secreted. The existence of two such forms is unusual in cell biology, and it remains to be determined why they have both been maintaine...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Pálsson E Tags: Biophys J Source Type: journals

Mathematical model of the Drosophila circadian clock: loop regulation and transcriptional integration.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Eukaryotic circadian clocks include interconnected positive and negative feedback loops. The clock-cycle dimer (CLK-CYC) and its homolog, CLK-BMAL1, are key transcriptional activators of central components of the Drosophila and mammalian circadian networks, respectively. In Drosophila, negative loops include period-timeless and vrille; positive loops include par domain protein 1. Clockwork orange (CWO) is a recently discovered negative transcription factor with unusual effects on period, timeless, vrille, and par domain protein 1. To understand the actions of this protein, we introduced a new system of ordinary differe...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Fathallah-Shaykh HM, Bona JL, Kadener S Tags: Biophys J Source Type: journals

Accounting for near-normal glucose sensitivity in Kir6.2[AAA] transgenic mice.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
K(ir)6.2[AAA] transgenic mouse islets exhibit mosaicism such that approximately 70% of the beta-cells have nonfunctional ATP-sensitive potassium (K(ATP)) channels, whereas the remainder have normal K(ATP) function. Despite this drastic reduction, the glucose dose-response curve is only shifted by approximately 2 mM. We use a previously published mathematical model, in which K(ATP) conductance is increased by rises in cytosolic calcium through indirect effects on metabolism, to investigate how cells could compensate for the loss of K(ATP) conductance. Compensation is favored by the assumption that only a small fraction ...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Tsaneva-Atanasova K, Sherman A Tags: Biophys J Source Type: journals

Retroviral assembly and budding occur through an actin-driven mechanism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The assembly and budding of a new virus is a fundamental step in retroviral replication. Yet, despite substantial progress in the structural and biochemical characterization of retroviral budding, the underlying physical mechanism remains poorly understood, particularly with respect to the mechanism by which the virus overcomes the energy barrier associated with the formation of high membrane curvature during viral budding. Using atomic force, fluorescence, and transmission electron microscopy, we find that both human immunodeficiency virus and Moloney murine leukemia virus remodel the actin cytoskeleton of their host....
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Gladnikoff M, Shimoni E, Gov NS, Rousso I Tags: Biophys J Source Type: journals

Simulation of spontaneous Ca2+ oscillations in astrocytes mediated by voltage-gated calcium channels.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The purpose of this computational study was to investigate the possible role of voltage-gated Ca(2+) channels in spontaneous Ca(2+) oscillations of astrocytes. By incorporating different types of voltage-gated Ca(2+) channels and a previous model, this study reproduced typical Ca(2+) oscillations in silico. Our model could mimic the oscillatory phenomenon under a wide range of experimental conditions, including resting membrane potential (-75 to -60 mV), extracellular Ca(2+) concentration (0.1 to 1500 muM), temperature (20 to 37 degrees C), and blocking specific Ca(2+) channels. By varying the experimental conditions, ...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Zeng S, Li B, Zeng S, Chen S Tags: Biophys J Source Type: journals

Lifetime and strength of periodic bond clusters between elastic media under inclined loading.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Focal adhesions are clusters of specific receptor-ligand bonds that link an animal cell to an extracellular matrix. To understand the mechanical responses of focal adhesions, here we develop a stochastic-elasticity model of a periodic array of adhesion clusters between two dissimilar elastic media subjected to an inclined tensile stress, in which stochastic descriptions of molecular bonds and elastic descriptions of interfacial traction are unified in a single modeling framework. We first establish a fundamental scaling law of interfacial traction distribution and derive a stress concentration index that governs the tr...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Qian J, Wang J, Lin Y, Gao H Tags: Biophys J Source Type: journals

Open-state occupancy prevents gating charge relaxation of N-type (CaV2.2) calcium channels.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
N-type and L-type channels have significant gating differences, and we wondered whether some of these differences are linked to the relationship between charge movement and channel opening. The time constants for N-channel closing (tau(Deact)) and Off-gating charge movement (tauQ(Off)) were compared over a range of voltages. tauQ(Off) was significantly larger than tau(Deact) at voltages < -10 mV, and the voltage dependence of the tauQ(Off) was less steep than that for tau(Deact), which suggests that gating charge relaxation does not limit channel closing. Roscovitine, a drug that slows N-channel closing by holding t...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Yarotskyy V, Elmslie KS Tags: Biophys J Source Type: journals

Gating transition of pentameric ligand-gated ion channels.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Pentameric ligand-gated ion channels are an important family of membrane proteins and play key roles in physiological processes, including signal transduction at chemical synapses. Here, we study the conformational changes associated with the opening and closing of the channel pore. Based on recent crystal structures of two prokaryotic members of the family in open and closed states, respectively, mixed elastic network models are constructed for the transmembrane domain. To explore the conformational changes in the gating transition, a coarse-grained transition path is computed that smoothly connects the closed and ope...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Zhu F, Hummer G Tags: Biophys J Source Type: journals

Energy transfer in light-adapted photosynthetic membranes: from active to saturated photosynthesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In bacterial photosynthesis light-harvesting complexes, LH2 and LH1 absorb sunlight energy and deliver it to reaction centers (RCs) with extraordinarily high efficiency. Submolecular resolution images have revealed that both the LH2:LH1 ratio, and the architecture of the photosynthetic membrane itself, adapt to light intensity. We investigate the functional implications of structural adaptations in the energy transfer performance in natural in vivo low- and high-light-adapted membrane architectures of Rhodospirillum photometricum. A model is presented to describe excitation migration across the full range of light inte...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Fassioli F, Olaya-Castro A, Scheuring S, Sturgis JN, Johnson NF Tags: Biophys J Source Type: journals

Helical conformation of the SEVI precursor peptide PAP248-286, a dramatic enhancer of HIV infectivity, promotes lipid aggregation and fusion.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In previous in vivo studies, amyloid fibers formed from a peptide ubiquitous in human seminal fluid (semen-derived enhancer of viral infection (SEVI)) were found to dramatically enhance the infectivity of the HIV virus (3-5 orders of magnitude by some measures). To complement those studies, we performed in vitro assays of PAP(248-286), the most active precursor to SEVI, and other polycationic polymers to investigate the physical mechanisms by which the PAP(248-286) promotes the interaction with lipid bilayers. At acidic (but not at neutral) pH, freshly dissolved PAP(248-286) catalyzes the formation of large lipid flocc...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Brender JR, Hartman K, Gottler LM, Cavitt ME, Youngstrom DW, Ramamoorthy A Tags: Biophys J Source Type: journals

Dielectric relaxation dynamics of water in model membranes probed by terahertz spectroscopy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We study hydrated model membranes, consisting of stacked bilayers of 1,2-dioleoyl-sn-glycero-3-phosphocholine lipids, using terahertz time-domain spectroscopy and infrared spectroscopy. Terahertz spectroscopy enables the investigation of water dynamics, owing to its sensitivity to dielectric relaxation processes associated with water reorientation. By controlling the number of water molecules per lipid molecule in the system, we elucidate how the interplay between the model membrane and water molecules results in different water dynamics. For decreasing hydration levels, we observe the appearance of new types of water ...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Tielrooij KJ, Paparo D, Piatkowski L, Bakker HJ, Bonn M Tags: Biophys J Source Type: journals

Sorting of lens aquaporins and connexins into raft and nonraft bilayers: role of protein homo-oligomerization.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Two classes of channel-forming proteins in the eye lens, the water channel aquaporin-0 (AQP-0) and the connexins Cx46 and Cx50, are preferentially located in different regions of lens plasma membranes (1,2). Because these membranes contain high concentrations of cholesterol and sphingomyelin, as well as phospholipids such as phosphatidylcholine with unsaturated hydrocarbon chains, microdomains (rafts) form in these membranes. Here we test the hypothesis that sorting into lipid microdomains can play a role in the disposition of AQP-0 and the connexins in the plane of the membrane. For both crude membrane fractions and p...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Tong J, Briggs MM, Mlaver D, Vidal A, McIntosh TJ Tags: Biophys J Source Type: journals

Synchronous in situ ATPase activity, mechanics, and Ca2+ sensitivity of human and porcine myocardium.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We examined flash-frozen left-ventricle human cardiomyocyte bundles from healthy donors to determine control parameters for isometric tension (P(o)) development and Ca(2+) sensitivity, while simultaneously measuring actomyosin ATPase activity in situ by a fluorimetric technique. P(o) was 17 kN m(-2) and pCa(50%) was 5.99 (28 degrees C, I = 130 mM). ATPase activity increased linearly with tension to 132 muM s(-1). To determine the influence of flash-freezing, we compared the same parameters in both glycerinated and flash-frozen porcine left-ventricle trabeculae. P(o) in glycerinated porcine myocardium was 25 kN m(-2), and m...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Griffiths PJ, Isackson H, Pelc R, Redwood CS, Funari SS, Watkins H, Ashley CC Tags: Biophys J Source Type: journals

Analysis of sub-tauc and supra-tauc motions in protein Gbeta1 using molecular dynamics simulations.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The functions of proteins depend on the dynamical behavior of their native states on a wide range of timescales. To investigate these dynamics in the case of the small protein Gbeta1, we analyzed molecular dynamics simulations with the model-free approach of nuclear magnetic relaxation. We found amplitudes of fast timescale motions (sub-tau(c), where tau(c) is the rotational correlation time) consistent with S(2) obtained from spin relaxation measurements as well as amplitudes of slow timescale motions (supra-tau(c)) in quantitative agreement with S(2) order parameters derived from residual dipolar coupling measurement...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Bui JM, Gsponer J, Vendruscolo M, Dobson CM Tags: Biophys J Source Type: journals

Tyrosine autofluorescence as a measure of bovine insulin fibrillation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The traditional approach to investigating the partial unfolding and fibrillation of insulin, and proteins at large, has involved use of the dyes 1-anilinonaphthalene-8-sulphonic acid (ANS) and Thioflavin T (ThT), respectively. We compare the kinetic profiles of ThT, ANS, light scattering, and intrinsic Tyr fluorescence during insulin fibrillation. The data reveal that the sequence of structural changes (dimers --> monomers --> partially unfolded monomers --> oligomeric aggregates --> fibrils) accompanying insulin fibrillation can be detected directly using intrinsic Tyr fluorescence. The results indicate th...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Bekard IB, Dunstan DE Tags: Biophys J Source Type: journals

Solution and crystal molecular dynamics simulation study of m4-cyanovirin-N mutants complexed with di-mannose.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cyanovirin-N (CVN) is a highly potent anti-HIV carbohydrate-binding agent that establishes its microbicide activity through interaction with mannose-rich glycoprotein gp120 on the virion surface. The m4-CVN and P51G-m4-CVN mutants represent simple models for studying the high-affinity binding site, B(M). A recently determined 1.35 A high-resolution structure of P51G-m4-CVN provided details on the di-mannose binding mechanism, and suggested that the Arg-76 and Glu-41 residues are critical components of high mannose specificity and affinity. We performed molecular-dynamics simulations in solution and a crystal environmen...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Vorontsov II, Miyashita O Tags: Biophys J Source Type: journals

Collective dynamics of periplasmic glutamine binding protein upon domain closure.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The glutamine binding protein is a vital component of the associated ATP binding cassette transport systems responsible for the uptake of glutamine into the cell. We have investigated the global movements of this protein by molecular dynamics simulations and principal component analysis (PCA). We confirm that the most dominant mode corresponds to the biological function of the protein, i.e., a hinge-type motion upon ligand binding. The closure itself was directly observed from two independent trajectories whereby PCA was used to elucidate the nature of this closing reaction. Two intermediary states are identified and d...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Loeffler HH, Kitao A Tags: Biophys J Source Type: journals

Multiple molecular dynamics simulations of TEM beta-lactamase: dynamics and water binding of the omega-loop.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Omega-loop of TEM beta-lactamase is involved in substrate recognition and catalysis. Its dynamical properties and interaction with water molecules were investigated by performing multiple molecular dynamics simulations of up to 50 ns. Protein flexibility was assessed by calculating the root mean-square fluctuations and the generalized order parameter, S(2). The residues in secondary structure elements are highly ordered, whereas loop regions are more flexible, which is in agreement with previous experimental observations. Interestingly, the Omega-loop (residues 161-179) is rigid with order parameters similar to sec...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Bös F, Pleiss J Tags: Biophys J Source Type: journals

Counteraction of urea by trimethylamine N-oxide is due to direct interaction.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Trimethylamine N-oxide (TMAO) is a naturally occurring osmolyte that stabilizes proteins, induces folding, and counteracts the denaturing effects of urea, pressure, and ice. To establish the mechanism behind these effects, isotopic substitution neutron-scattering measurements were performed on aqueous solutions of TMAO and 1:1 TMAO-urea at a solute mole fraction of 0.05. The partial pair distribution functions were extracted using the empirical potential structure refinement method. The results were compared with previous results obtained with isosteric tert-butanol, as well as the available data from spectroscopy and ...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Meersman F, Bowron D, Soper AK, Koch MH Tags: Biophys J Source Type: journals

Application of fluorescence spectroscopy to quantify shear-induced protein conformation change.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Rapid and robust methods are required to quantify the effect of hydrodynamic shear on protein conformation change. We evaluated such strategies in this work and found that the binding of the fluorescent probe 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid (bis-ANS) to hydrophobic pockets in the blood protein von Willebrand factor (VWF) is enhanced upon the application of fluid shear to the isolated protein. Significant structural changes were observed when the protein was sheared at shear rates >or= 6000/s for approximately 3.5 min. The binding of bis-ANS to multimeric VWF, but not dimeric VWF or control protei...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Themistou E, Singh I, Shang C, Balu-Iyer SV, Alexandridis P, Neelamegham S Tags: Biophys J Source Type: journals

Large structural change in isolated synaptic vesicles upon loading with neurotransmitter.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The size of a synaptic vesicle (SV) is generally thought to be determined by the amount of lipid and membrane protein it contains. Once formed, it is thought to remain constant in size. Using fluorescence correlation spectroscopy and cryogenic electron microscopy, we show that glutamatergic vesicles reversibly increase their size upon filling with glutamate. The increase ( approximately 25% in diameter) corresponds to an increase in surface area of approximately 50% and in volume of approximately 100%. This large size increase implies a large structural change in the SV upon loading with neurotransmitters. Vesicles lac...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Budzinski KL, Allen RW, Fujimoto BS, Kensel-Hammes P, Belnap DM, Bajjalieh SM, Chiu DT Tags: Biophys J Source Type: journals

Human serum albumin inhibits Abeta fibrillization through a "monomer-competitor" mechanism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Human serum albumin (HSA) is not only a fatty acid and drug carrier protein, it is also a potent inhibitor of Abeta self-association in plasma. However, the mechanism underlying the inhibition of Abeta fibrillization by HSA is still not fully understood. We therefore investigated the Abeta-HSA system using a combined experimental strategy based on saturation transfer difference (STD) NMR and intrinsic albumin fluorescence experiments on three Abeta peptides with different aggregation propensities (i.e., Abeta(12-28), Abeta(1-40), and Abeta(1-42)). Our data consistently show that albumin selectively binds to cross-beta-...
Source: Biophysical Journal - November 4, 2009 Category: Physics Authors: Milojevic J, Raditsis A, Melacini G Tags: Biophys J Source Type: journals