Channels Of Different Lengths Research Articles

Amphiphile-Regulation of Ion Channel Function by Changes in a Transferable Lipid Bilayer Spring Constant

Amphiphilic compounds regulate membrane protein function by specific chemical interactions with their target receptor, as well as by adsorbing to and altering the physical properties of the host lipid bilayer, and thus the energetic cost of bilayer deformations associated with protein conformational changes at the protein-bilayer interface. Specific regulatory mechanisms may be investigated using well-described methodologies of ligand-receptor interactions. But the bilayer-mediated regulation, due to lack of transferable parameters to describe the complex effects of amphiphiles on the bilayer physical properties, has not matured into a quantitative, predictive field of science - which is problematic considering its ubiquitous consequences in biological research. Using measurements of the effects of amphiphiles on the lifetime of gramicidin (gA) channels of different lengths, we show that the net effects of amphiphiles, on the energetic cost of the bilayer deformation associated with a change in length of the bilayer-spanning part of an embedded protein, can be a characterized as changes in a phenomenological spring constant that summarizes the bilayer elastic properties. Moreover, amphiphile-induced changes in the spring constant, as measured using gA channels of a given length, are transferable and can be used to predict the effects of amphiphiles on the function of gA channels of another length, as well as on the gating of voltage-dependent sodium channels in living cells.

Investigating the Effects of Acylated Lactoferricin Peptides on the Properties of Lipid Bilayers Using Gramicidin A Channels as Probes

Lactoferricin is an anti-bacterial peptide that is released from the iron-binding glycoprotein lactoferrin through enzymatic cleavage by pepsin. Lactoferricin is found mainly in milk and secreted fluids such as tears, saliva, bronchial mucus and seminal fluid, and it plays an important and multi-functional role in host defense, as it is part of the body's primary defense against bacteria, fungi, protozoa and viruses. It also has antitumor and immunological effects. Previous studies show that lactoferricin may inhibit bacterial growth by two different mechanisms: by sequestering the iron necessary for bacterial nutrition; and by adsorbing to bacterial plasma membranes, which may disrupt the membrane barrier properties or some other membrane function. Lactoferricin indeed permeabilizes bacterial membranes, but it remains unclear whether this is the primary mechanism by which it exerts its anti-bacterial activity. We therefore explored whether lactoferricin analogues could alter other bilayer properties, using gramicidin A (gA) channels of different lengths as probes. Specifically, could the lactoferricins alter lipid bilayer elasticity or intrinsic curvature. We tested two amino acylated lactoferricin derivatives, NC2-LfB-1MeTrp5 and NC4-LfB-1MeTrp5 (with the sequences Ac-R-R-W-Q-MeW-R-NH2 and Bu-R-R-W-Q-MeW-R-NH2). Both compounds increase gA channel appearance rates and lifetimes, meaning that they decrease bilayer stiffness, at concentrations (1-10 μM) where they do not cause a breakdown of lipid bilayer barrier properties. Because they had similar effects on the lifetimes of the long and short channels, we conclude that the lactoferricins alter lipid intrinsic curvature.

The Insulin-sensitizers Troglitazone And Rosiglitazone Alter Lipid Bilayer Properties

Thiazolidinediones are widely used to treat hyperglycemia in patients suffering from type 2 diabetes. Three thiazolinediones - troglitazone (Resulin), rosiglitazone (Avandia), and pioglitazone (Actos) - have been marketed; troglitazone was subsequently withdrawn due to hepatotoxicity. The thiazolidinediones are selective peroxizome-proliferator receptor gamma (PPARγ) agonists and they increase insulin sensitivity. They also have been found to have anti-oxidant, anti-inflammatory, anti-atherosclerotic and cardiovascular effects, but PPARγ activation alone does not account for all their actions. All three derivatives, with troglitazone being the most potent, modulate L-type calcium and delayed-rectifier potassium Kv1.3 channels by a seemingly PPARγ-independent mechanism. This could result from the adsorption of amphiphilic molecules to the membrane, which can alter bilayer properties such as thickness, intrinsic curvature and elastic moduli, and thus membrane protein function. We therefore set out to determine whether the amphiphilic troglitazone and rosiglitazone alter lipid bilayer properties. Using gramicidin channels as probes, where we monitor the changes in channel lifetime and rate of appearance, we tested and compared the effects of troglitazone and rosiglitazone on channels of different lengths in DOPC bilayers. Troglitazone or rosiglitazone did not alter gramicidin channel conductances, suggesting that direct interactions are not involved. In contrast, the lifetimes of both channels increased with similar relative changes for both the shorter and the longer channels. Consistent with their effects on calcium and potassium channels troglitazone is more potent than rosiglitazone. Our results show that both troglitazone and rosiglitazone affect bulk membrane properties at the concentrations where they modulate other ion channels.

Invariance of Single-File Water Mobility in Gramicidin-like Peptidic Pores as Function of Pore Length

We investigated the structural and energetic determinants underlying water permeation through peptidic nanopores, motivated by recent experimental findings that indicate that water mobility in single-file water channels displays nonlinear length dependence. To address the molecular mechanism determining the observed length dependence, we studied water permeability in a series of designed gramicidin-like channels of different length using atomistic molecular dynamics simulations. We found that within the studied range of length the osmotic water permeability is independent of pore length. This result is at variance with textbook models, where the relationship is assumed to be linear. Energetic analysis shows that loss of solvation rather than specific water binding sites in the pore form the main energetic barrier for water permeation, consistent with our dynamics results. For this situation, we propose a modified expression for osmotic permeability that fully takes into account water motion collectivity and does not depend on the pore length. Different schematic barrier profiles are discussed that explain both experimental and computational interpretations, and we propose a set of experiments aimed at validation of the presented results. Implications of the results for the design of peptidic channels with desired permeation characteristics are discussed.

Bursts in single-file motion mediated conduction

We present a cellular automaton (CA) model of particles in a single-file motion with free particle exchange at the boundaries of a one-dimensional channel connected to two infinite reservoirs in order to study the self-transmission of particles with excluded mutual passage. The parallel, local and homogeneous rule sets of the CA algorithm consider two different interactions of varying strength between particles, without any specific particle-channel interaction. CA model results suggest that one hallmark of single-file motion is the conduction bursts at a particular time scale, which have thus far only been discovered for hydrogen bond networked water translocation. The cumulative transport probabilities of particles through single-file channels of different length follow a single profile, which can be obtained through proper scaling of time. The universal features of our results suggest new experiments in single-file channel with fluids other than water.

2,3-Butanedione Monoxime Affects Cystic Fibrosis Transmembrane Conductance Regulator Channel Function through Phosphorylation-Dependent and Phosphorylation-Independent Mechanisms: The Role of Bilayer Material Properties

2,3-Butanedione monoxime (BDM) is widely believed to act as a chemical phosphatase. We therefore examined the effects of BDM on the cystic fibrosis transmembrane regulator (CFTR) Cl(-) channel, which is regulated by phosphorylation in a complex manner. In guinea pig ventricular myocytes, forskolin-activated whole-cell CFTR currents responded biphasically to external 20 mM BDM: a rapid approximately 2-fold current activation was followed by a slower (tau approximately 20 s) inhibition (to approximately 20% of control). The inhibitory response was abolished by intracellular dialysis with the phosphatase inhibitor microcystin, suggesting involvement of endogenous phosphatases. The BDM-induced activation was studied further in Xenopus laevis oocytes expressing human epithelial CFTR. The concentration for half-maximal BDM activation (K(0.5)) was state-dependent, approximately 2 mM for highly and approximately 20 mM for partially phosphorylated channels, suggesting a modulated receptor mechanism. Because BDM modulates many different membrane proteins with similar K(0.5) values, we tested whether BDM could alter protein function by altering lipid bilayer properties rather than by direct BDM-protein interactions. Using gramicidin channels of different lengths (different channel-bilayer hydrophobic mismatch) as reporters of bilayer stiffness, we found that BDM increases channel appearance rates and lifetimes (reduces bilayer stiffness). At 20 mM BDM, the appearance rates increase approximately 4-fold (for the longer, 15 residues/monomer, channels) to approximately 10-fold (for the shorter, 13 residues/monomer channels); the lifetimes increase approximately 50% independently of channel length. BDM thus reduces the energetic cost of bilayer deformation, an effect that may underlie the effects of BDM on CFTR and other membrane proteins; the state-dependent changes in K(0.5) are consistent with such a bilayer-mediated mechanism.

Manipulating lipid bilayer material properties using biologically active amphipathicmolecules

Lipid bilayers are elastic bodies with properties that can be manipulated/controlledby the adsorption of amphipathic molecules. The resulting changes in bilayerelasticity have been shown to regulate integral membrane protein function. To furtherunderstand the amphiphile-induced modulation of bilayer material properties(thickness, intrinsic monolayer curvature and elastic moduli), we examined howan enantiomeric pair of viral anti-fusion peptides (AFPs)—Z–Gly–D-Phe andZ–Gly–Phe, where Z denotes a benzyloxycarbonyl group, as well as Z–Phe–Tyr andZ–D-Phe–Phe–Gly—alters the function of enantiomeric pairs of gramicidin channels ofdifferent lengths in planar bilayers. For both short and long channels, the channellifetimes and appearance frequencies increase as linear functions of the aqueous AFPconcentration, with no apparent effect on the single-channel conductance. Thesechanges in channel function do not depend on the chirality of the channels orthe AFPs. At pH 7.0, the relative changes in channel lifetimes do not vary whenthe channel length is varied, indicating that these compounds exert their effectsprimarily by causing a positive-going change in the intrinsic monolayer curvature. AtpH 4.0, the AFPs are more potent than at pH 7.0 and have greater effects on theshorter channels, indicating that these compounds now change the bilayer elasticmoduli. When AFPs of different anti-fusion potencies are compared, the rankorder of the anti-fusion activity and the channel-modifying activity is similar,but the relative changes in anti-fusion potency are larger than the changes inchannel-modifying activity. We conclude that gramicidin channels are useful as molecularforce transducers to probe the influence of small amphiphiles upon lipid bilayer materialproperties.

Effect of the Location of the Inlet and Outlet Structures on Short-Circuiting: Experimental Investigation

The location of the inlet and outlet structures in a treatment plant (e.g., waste stabilization pond) may affect its hydraulic efficiency by increasing short-circuiting. Therefore, in this paper, the effect of the location of inlet and outlet structures was investigated in three laboratory channels of different lengths. Nine different combinations of inlet and outlet locations were considered for each channel under varying rates of flow. Results showed that the placement of the inlet and outlet structures close to the surface and the bottom of the pond, respectively, gave the minimum value of short-circuiting. This location was, therefore, judged to be the optimum among the nine combinations considered. The short-circuiting index was found to increase both with the dispersion number and the actual flow velocity, giving correlation coefficients of 0.3186 to 0.9258 and 0.8057 to 0.9972, respectively. Although minimization of short-circuiting will result in higher hydraulic efficiency, it may not necessarily result in higher effluent quality unless the temporal and vertical fluctuations of the water column are also considered.

The Effect of Channel Length on the Residual Circulation in Tidally Dominated Channels

Abstract With an analytic model, this paper describes the subtidal circulation in tidally dominated channels of different lengths, with arbitrary lateral depth variations. The focus is on an important parameter associated with the reversal of the exchange flows. This parameter (δ) is defined as the ratio between the channel length and one-quarter of the tidal wavelength, which is determined by water depth and tidal frequency. In this study, a standard bottom drag coefficient, CD = 0.0025, is used. For a channel with δ smaller than 0.6–0.7 (short channels), the exchange flow at the open end has an inward transport in deep water and an outward transport in shallow water. This situation is just the opposite of channels with a δ value larger than 0.6–0.7 (long channels). For a channel with a δ value of about 0.35–0.5, the exchange flow at the open end reaches the maximum of a short channel. For a channel with a δ value of about 0.85–1.0, the exchange flow at the open end reaches the maximum of a long channel, with the inward flux of water occurring over the shoal area and the outward flow in the deep-water area. However, near the closed end of a long channel, the exchange flow appears as that in a short channel—that is, the exchange flow changes direction along the channel from the head to the open end of the channel. For a channel with a δ value of about 0.6–0.7, the tidally induced subtidal exchange flow at the open end reaches its minimum when there is little flow across the open end and the water residence time reaches its maximum. The mean sea level increases toward the closed end for all δ values. However, the spatial gradient of the mean sea level in a short channel is much smaller than that of a long channel. The differences between short and long channels are caused by a shift in dynamical balance of momentum or, equivalently, a change in tidal wave characteristics from a progressive wave to a standing wave.

Scale dependent effects of predatory fish on stream benthos

In open predation experiments the effects of predators on prey densities can be influenced by predator consumption and by prey movements in to and out of experimental arenas. A published model predicts that the predator effects observed in such experiments are scale dependent over the scale range where there is a transition from movement control (of prey densities) to consumption control. The scale dependence follows from the assumption that per capita rate of emigration out of an experimental arena decreases with increasing arena size.To test this model the effects of a small benthic fish (Cottus gobio) on densities of stream invertebrates was investigated in instream channels of different length (0.5, 2 and 8 m). The effect of fish predation was scale dependent for four prey taxa. For three of these taxa predator effects increased with experimental scale, which is in agreement with model predictions. However, this proved to be a case of “making the right prediction for the wrong reason” as the basic assumption of scale dependent emigration rate was not upheld. By analyzing the behaviour of the model, parameterized with emigration and consumption rates observed in the experimental channels, it was found that observed scale effects occurred because prey emigration in response to the predator treatment was modified by the experimental scale. Further analysis of the parameterized model suggested that the densities of most prey taxa were controlled by prey movements and not by consumption by the sculpins.

Monte Carlo studies of two dimensional transport in GaN/AlGaN transistors: Comparison with transport in AlGaAs/GaAs channels

In this communication we report results on Monte Carlo transport studies in GaN/AlGaN two dimensional electron gas. In addition to steady state results we examine transit times in channels of different lengths under various bias conditions. The results are compared to those calculated for the GaAs/AlGaAs device. We find that at low electric fields, transit time in the GaN channel can be considerably longer than the time in a GaAs channel. This is attributed to the overshoot effect in the GaAs channel. However, at large electric field transport the transit times in GaN and GaAs channel are found to be comparable.

Dynamics of the Coastal Transition Zone jet: 2. Nonlinear finite amplitude behavior

The finite amplitude nonlinear behavior of the coastal transition zone (CTZ) jet, assumed to be governed by quasi‐geostrophic dynamics, is studied utilizing numerical experiments in an idealized geometry. Finite difference solutions to initial value problems are obtained for a stratified, six‐layer fluid in a periodic, flat bottom, ƒ plane channel. The initial flow field in all experiments includes a uniform along‐channel jet with horizontal and vertical structure obtained from CTZ hydrographic and current measurements made in May 1987. The maximum velocity in the jet is about 0.5 m s−1, the vertical shear is such that the velocities below 500 m depth are small, and the jet width is about 60 km. The Rossby radius for the first baroclinic mode is 24.6 km. An analysis of the linear stability of the jet flow field in part 1 shows that the jet is linearly unstable to disturbances with along‐jet wavelengths greater than 50 km. The largest growth rate is found for a wavelength around 260 km. The objectives here are to find the characteristics of the finite amplitude nonlinear jet instabilities and to examine local dynamical balances for signatures of instability processes that would help with the physical interpretation of results from limited‐area CTZ data assimilation models. Experiments are run with periodic channels of different length L(x), where the initial flow includes the basic jet and a small perturbation in the form of the most unstable linear mode for a wavelength equal L(x). In the basic experiment (BC) L(x) = 250 km. One experiment (LC) is run in a long channel L(x) = 1280 km with initial disturbances forced by application of a weak wind stress curl for three days. For times less than about 70 days, experiments BC and LC show the growth and development of finite amplitude meanders in the CTZ jet with spatial variations similar to those observed in spring 1987. During this early time period, the amplitudes of the meanders grow at rates of 1–4 km d−1, increasing with meander amplitude, and the meanders propagate in the direction of the jet upper layer flow at phase velocities of 5–3 km d−1, decreasing with meander amplitude. Initially, at small amplitudes the instability involves comparable contributions from barotropic and baroclinic processes in agreement with linear theory, but for large amplitude meanders the baroclinic energy conversion processes dominate. The vertical velocity field develops a characteristic spatial structure in relation to the jet meanders as do terms in the kinetic energy balance corresponding to the time rate of change of kinetic energy following fluid particles and to the rate of conversion from potential energy. The spatial structure of the latter field may provide a useful indication for jet baroclinic instability processes in limited‐area models. At later times in experiment BC (days 90–110), the meander growth is limited by a pinching‐off process that results in the formation of detached eddies on both sides of the jet. This process is characterized by a large relative increase of the kinetic energy in the lower layers and in the depth‐independent component of the flow. Experiments with L(x) = 180 and 150 km give qualitatively different behavior than that found in experiments BC and LC. The meander growth is bounded, and the jet flow field exhibits time‐dependent variations in the volume integrated kinetic and potential energies. For large time the flow may asymptotically approach a nearly steady state or states with irregular or nearly periodic oscillations in the integrated kinetic and potential energies.

Possible Use of Magnetic Fields in Determining Pore Geometry of Porous Media

Abstract Simplified models, consisting of single, circular channels and channels of different length and diameter in series and parallel combinations, are used in conjunction with the equations of Poiseuille and Hartmann to demonstrate the dependence of the rate of flow of mercury in the models on channel dimensions when the models are subjected to transverse magnetic fields. Experimental tests conducted on mercury-saturated, glass-bead packs and a natural rock sample show that a magnetic field applied transversely to the direction of flow retards flow rate. The magnitude of the magnetic effect increased with increasing bead size and field intensity. Results of this work suggest that magnetic fields have potential in the study of the internal geometry of flow channels in porous media. Introduction The purpose of this work is to determine qualitatively by theoretical and experimental considerations whether or not a magnetic method has potential in the study of the basic properties of rock. The nature of the solid surface and the geometry of the pore network in petroleum-bearing rock plays an important role in the flow behavior of fluids in a petroleum reservoir. Hence, any technique of study that would provide new and additional information on the rock matrix would contribute to a better understanding of petroleum reservoir performance. One such technique appearing to offer performance. One such technique appearing to offer promise is in the area of magnetohydrodynamics. promise is in the area of magnetohydrodynamics. While much research, both theoretical and experimental, has been devoted to the problems concerned with the flow of conducting fluids in transverse magnetic fields in single channels, very little information has been published regarding the behavior of conducting liquids in porous media under the influence of a transverse magnetic field. Perhaps this dearth of information can be attributed Perhaps this dearth of information can be attributed to two main causes: (1) the pores and pore connections are generally so small that intense magnetic fields are required to produce Hartmann numbers of sufficient magnitude to exert appreciable influence on flow rate, and (2) the extreme complexity of the channel systems in porous media render them intractable to theoretical analysis unless numerous assumptions are made to simplify network geometry. When a conducting fluid moves in a channel in a transverse magnetic field, a force is exerted on the fluid which retards its flow. The magnitude of flow-rate retardation increases with increasing field intensity, channel dimensions and channel-wall conductivity. These magnetohydrodynamic phenomena and theory have been described and developed by various investigators. Since a petroleum reservoir rock is an interconnected network of pores and channels within a rock framework, one would anticipate that the geometry of the network would exert some influence on the magnitude of the effect of a transverse magnetic field on the rate of flow of a conducting fluid therein. The purpose of this work is to demonstrate through the use of simple models and experimental data that the magnetic field effect on flow rate has potential for use in determining size and size potential for use in determining size and size distribution of pores in porous materials.