Fluid mechanical and electrostatic study on the osmotic flow through cylindrical pores

When two solutions differing in solute concentration are separated by a porous membrane, the osmotic pressure will generate a net volume flux of the suspending fluid across the membrane; this is termed osmotic flow. We consider the osmotic flow across a membrane with circular cylindrical pores when the solute and the pore walls are electrically charged, and the suspending fluid is an electrolytic solution containing small cations and anions. Under the condition in which the radius of the pores and that of the solute molecules greatly exceed those of the solvent as well as the ions, a fluid mechanical and electrostatic theory is introduced to describe the osmotic flow in the presence of electric charge. The interaction energy, including the electrostatic interaction between the solute and the pore wall, plays a key role in determining the osmotic flow. We examine the electrostatic effect on the osmotic flow and discuss the difference in the interaction energy determined from the nonlinear Poisson-Boltzmann equation and from its linearized equation (the Debye-Hückel equation).     

Interfacial barriers to gas transport: probing solid-gas interfaces at the atomistic level

ABSTRACT

An understanding of interfacial barriers underpinning fluid transport in nanoporous membranes is critical for the design of efficient next generation membranes, to harness their potential for industrial scale separations. Such barriers include the contribution of external and internal interfacial barriers, and strongly depend on smoothness of the pore surface, pore size, shape, tortuosity, structural defects such as pore blockage and thermodynamic state of the fluid. We review recent progress in the transport of a fluid through nanoporous membrane materials such as zeolites and carbon nanotubes, which hold promise for industrial significance, but their application is subject to strong interfacial barriers. The contribution of interfacial barriers to the overall transport in these membrane materials is found to be particularly significant when the pore surface is uniform as well as at low temperatures and pressures. Further, such barriers that arise from internal defects such as grain boundaries are found to be remarkable and detrimental to separation kinetics. The internal interfacial barriers are found to be significant, and are enhanced when a dense medium such as a polymer is present at the interface, suggesting that interfacial barriers can play a key role in mixed matrix membranes and is an important area requiring further attention.     

Towards mimicking natural protein channels with aligned carbon nanotube membranes for active drug delivery

AimsCarbon nanotube (CNT) membranes offer an exciting opportunity to mimic natural protein channels due to 1) a mechanism of dramatically enhanced fluid flow 2) ability to place ‘gatekeeper’ chemistry at the entrance to pores 3) the ability for biochemical reactions to occur on gatekeeper molecules and 4) an ability to chemically functionalize each side of the membrane independently.Main methodsAligned CNT membranes were fabricated and CNT pore entrances modified with gatekeeper chemistry. Pressure driven fluid flow and diffusion experiments were performed to study the mechanisms of transport through CNTs.Key findingsThe transport mechanism through CNT membranes is primarily 1) ionic diffusion near bulk expectation 2) gas flow enhanced 1–2 orders of magnitude primarily due to specular reflection 3) fluid flow 4–5 orders of magnitude faster than conventional materials due to a nearly ideal slip-boundary interface. The transport can be modulated by ‘gatekeeper’ chemistry at the pore entrance using steric hindrance, electrostatic attraction/repulsion, or biochemical state. The conformation of charged tethered molecules can be modulated by applied bias setting the stage for programmable drug release devices.SignificanceThe membrane structure is mechanically far more robust than lipid bilayer films, allowing for large-scale chemical separations, delivery or sensing based on the principles of protein channels. The performance of protein channels is several orders of magnitude faster than conventional membrane materials. The fundamental requirements of mimicking protein channels are present in the CNT membrane system.     

Factors affecting membrane fouling in filtration of Saccharomyces cerevisiae in an internal ceramic filter bioreactor

Filtration of ethanol fermentation medium and broth by using symmetric and asymmetric ceramic membranes has been studied in an internal filter bioreactor. Factors studied included membrane structure and pore size, medium sterilization, and concentrations of glucose, yeast extract in the medium, yeast cell and protein in broth. The aim was to determine the main factors responsible for the decline in filtration performance during ethanol fermentation by Saccharomyces cerevisiae. Flux index (Fi) of a new concept has been developed to evaluate the degree of flux decline during the membrane fouling process. Fi was defined as the ratio of the membrane flux at certain filtration time (t?=?t) to the initial (t?=??0) flux of pure water, not the initial (t?=?+0) flux of the test fluid. Flux with sterilized medium was approximately two-fold higher than that with unsterilized medium although the reason could not be explained clearly. Glucose, interaction between glucose and yeast extract, yeast cells, and proteins in fermentation broth were found to play an important part in membrane fouling. Fi of the symmetric membrane decreased to a less extent than that of the asymmetric membrane with increasing glucose concentration. But, the result with various yeast cell concentrations turned out to be contrary. Fouling was more serious for asymmetric membrane during the filtration of fermentation supernatant. This was thought to be due to different fouling mechanisms for the two types of membrane.     

Combined Diffusive and Viscous Transport of Methane in a Carbon Slit Pore

Abstract

The transport of mass through porous materials can occur by essentially two different mechanisms: (1) diffusion and (2) viscous flow. The former occurs when there is a gradient in chemical potential of the pore fluid, while the latter occurs in the presence of a pressure gradient. In general, fluid transport occurs by both of these mechanisms and their respective contributions to the total intra-pore flux are approximately additive. Experimentally, there is no unambiguous way of determining the individual contributions to the total flux of these two modes of transport. Fortunately, molecular simulations does provide a solution.

We present a novel simulation method in which the separate contributions to the total flux are determined. The method involves the use of two non-equilibrium molecular dynamics techniques: dual control volume grand canonical molecular dynamics (DCV GCMD) and an algorithm for simulating planar Poiseuille flow. We apply this technique to study the combined (viscous and diffusive) transport of methane through single slit-shaped graphite pores of width 2.5, 5.0 and 10.0 methane diameters. We find that the viscous contribution to the total intrapore flux through each of these pores is 10%, 15% and 34%, respectively.     

Molecular simulation for separation of ethylene and ethane by functionalised graphene membrane

ABSTRACT

Graphene is an excellent adsorbent and a membrane material for separation which has attracted wide attention in recent years. Moreover, compared with typical polymer materials, porous graphene has exhibited superior performance. In this paper, molecular dynamics and quantum mechanics were used to explore the appropriate pore size and separation mechanism of graphene. The 2N-Pore-13 (modified by N and H atom) membrane can prevent the penetration of ethane while maintaining high ethylene flux. The permeation rate of ethylene reached 3.7×10⁶ GPU in 5N-Pore-13 membrane, while the one of ethane was only 227 GPU. The mechanism is based on the fact that molecular structure of ethylene is two-dimensional, so that ethylene can get closer to membrane surface when it is adsorbed. When passing through the pores, ethylene has lower enthalpy and entropy barrier.     

Movement of the S4 segment in the hERG potassium channel during membrane depolarization

Abstract

The hERG potassium channel is a member of the voltage gated potassium (Kv) channel family, comprising a pore domain and four voltage sensing domains (VSDs). Like other Kv channels, the VSD senses changes in membrane voltage and transmits the signal to gates located in the pore domain; the gates open at positive potentials (activation) and close at negative potentials, thereby controlling the ion flux. hERG, however, differs from other Kv channels in that it is activated slowly but inactivated rapidly – a property that is crucial for the role it plays in the repolarization of the cardiac action potential. Voltage-gating requires movement of gating charges across the membrane electric field, which is accomplished by the transmembrane movement of the fourth transmembrane segment, S4, of the VSD containing the positively charged arginine or lysine residues. Here we ask if the functional differences between hERG and other Kv channels could arise from differences in the transmembrane movement of S4. To address this, we have introduced single cysteine residues into the S4 region of the VSD, expressed the mutant channels in Xenopus oocytes and examined the effect of membrane impermeable para-chloromercuribenzene sulphonate on function by the two-electrode voltage clamp technique. Our results show that depolarization results in the accessibility of seven consecutive S4 residues, including the first two charged residues, K525 and R528, to extracellularly applied reagent. These data indicate that the extent of S4 movement in hERG is similar to other Kv channels, including the archabacterial KvAP and the Shaker channel of Drosophila.     

Fusion pore stability of peptidergic vesicles

Abstract

It is believed that in regulated exocytosis the vesicle membrane fuses with the plasma membrane in response to a physiological stimulus. However, in the absence of stimulation, repetitive transient fusion events are also observed, reflecting a stable state. The mechanisms by which the initial fusion pore attains stability are poorly understood. We modelled energetic stability of the fusion pore by taking into account the anisotropic, intrinsic shape of the membrane constituents and their in-plane ordering in the local curvature of the membrane. We used cell-attached membrane capacitance techniques to monitor the appearance and conductance of single fusion pore events in cultured rat lactotrophs. The results revealed a bell-shaped distribution of the fusion pore conductance with a modal value of 25 pS. The experimentally observed increase of the fusion pore stability with decreasing fusion pore radius agrees well with the theoretical predictions. Moreover, the results revealed a correlation between the amplitude of transient capacitance increases and the fusion pore conductance, indicating that larger vesicles may attain a stable fusion pore with larger fusion pore diameters.     

The larval midgut of the cassava hornworm (Erinnyis ello)

Summary Columnar cells of the larval midgut of the cassava hornworm, Erinnyis ello, display microvilli with vesicles pinching off from their tips (anterior and middle midgut) or with a large number of double membrane spheres budding along their length (posterior midgut). Basal infoldings in columnar cells occur in a parallel array with many openings to the underlying space (posterior midgut) or are less organized with few openings (anterior and middle midgut). Goblet cells have a cavity, which is formed by invagination of the apical membrane and which occupies most of the cell (anterior and middle midgut) or only its upper part (posterior midgut). The infolded apical membrane shows modified microvilli, which sometimes (posterior midgut) or always (anterior and middle midgut) contain mitochondria. The cytoplasmic side of the membrane of the microvilli that contain mitochondria are studded with small particles. The results suggest that the anterior and middle region of the midgut absorbs water, whereas the posterior region secretes it. This results in a countercurrent flux of fluid, which is responsible for the enzyme recovery from undigested food before it is expelled. Intermediary and final digestion of food probably occur in the columnar cells under the action of plasma membrane-bound and glycocalix-associated enzymes.     

Hydrophobic segment of dengue virus C protein. Interaction with model membranes

Abstract

Dengue virus (DENV) C protein is essential for viral assembly. DENV C protein associates with intracellular membranes through a conserved hydrophobic domain and accumulates around endoplasmic reticulum-derived lipid droplets which could provide a platform for capsid formation during assembly. In a previous work we described a region in DENV C protein which induced a nearly complete membrane rupture of several membrane model systems, which was coincident with the theoretically predicted highly hydrophobic region of the protein. In this work we have carried out a study of the binding to and interaction with model biomembranes of a peptide corresponding to this DENV C region, DENV2_C6. We show that DENV2_C6 partitions into phospholipid membranes, is capable of rupturing membranes even at very low peptide-to-lipid ratios and its membrane-activity is modulated by lipid composition. These results identify an important region in the DENV C protein which might be directly implicated in the DENV life cycle through the modulation of membrane structure.     

Pore patterns on nuclear membranes

The pore patterns on a large number of nuclear and one non-nuclear membrane have been examined. Important qualitative features of the arrangement of pores can be described by computing a statistical measure, the radial distribution function, of the pore patterns. This measure distinguishes three different pore patterns:

1. 1. Clumped patterns in which pores are found in clusters which are widely separated from one another.

2. 2. Patterns in which there is only a short range inhibitory region surrounding each pore with no evidence of a long range ordering.

3. 3. Patterns in which there is a local ordering in the region surrounding each pore, extending to several times the mean interpore spacing.

Physical mechanisms which can lead to each of the observed patterns are discussed.     

Protective action of tamoxifen on carboxyatractyloside-induced mitochondrial permeability transition

AimsMitochondrial permeability transition is established after massive Ca²⁺ accumulation inside the matrix, in addition to an inducer. The closure of the pore can be accomplished by adenosine diphosphate and the immunosuppressant cyclosporin A. Recently, the estrogen antagonist, tamoxifen, has been introduced as an inhibitor of the opening of the permeability transition pore. However, the mechanism by which this drug inhibits pore opening is still under discussion. This work was performed with the purpose of establishing the membrane system involved in tamoxifen-induced pore closure. For this purpose, permeability transition was induced after the addition of carboxyatractyloside, which is a specific reagent that interacts with the adenine nucleotide translocase.Main methodsPermeability transition was assessed by analyzing matrix Ca²⁺ release, transmembrane electric gradient, and mitochondrial swelling in aged, as well as in freshly prepared mitochondria. Also, cytochrome c content was analyzed in membrane mitochondria as well as in the supernatant.Key findingsIn freshly prepared mitochondria, tamoxifen, at the concentration of 10 μM, totally inhibited nonspecific membrane permeability induced by 1 μM carboxyatractyloside. In addition, tamoxifen inhibited non-specific permeability in aged mitochondria and diminished membrane fluidity.SignificancePlausibly, the inhibitory effect of tamoxifen on nonspecific membrane permeability, as induced by carboxyatractyloside, should be ascribed to a diminution, of membrane fluidity by this drug.     

Shear stress induced lipid order and permeability changes of giant unilamellar vesicles

BackgroundThe permeability of a lipid bilayer is a function of its phase state and depends non-linearly on thermodynamic variables such as temperature, pressure or pH. We investigated how shear forces influence the phase state of giant unilamellar vesicles and their membrane permeability.MethodsWe determined the permeability of giant unilamellar vesicles composed of different phospholipid species under shear flow in a tube at various temperatures around and far off the melting point by analyzing the release of fluorescently labelled dextran. Furthermore, we quantified phase state changes of these vesicles under shear forces using spectral decomposition of the membrane embedded fluorescent dye Laurdan.ResultsWe observed that the membrane permeability follows a step function with increasing permeability at the transition from the gel to the fluid phase and vice versa. Second, there was an all-or-nothing permeabilization near the main phase transition temperature and a gradual dye release far off the melting transition. Third, the Laurdan phase state analysis suggests that shear forces induce a reversible melting temperature shift in giant unilamellar vesicle membranes.Major conclusionsThe observed effects can be explained best in a scenario in which shear forces directly induce membrane pores that possess relatively long pore lifetimes in proximity to the phase transition.General significanceOur study elucidates the release mechanism of thermo-responsive drug carriers as we found that liposome permeabilization is not continuous but quantized. Furthermore, the shear force induced melting temperature shift must be taken into consideration when thermo-responsive liposomes are designed.     

How does Amphotericin B Work?: Studies on Model Membrane Systems

Abstract

The drug Amphotericin B is a very important antifungal agent as well as one of the first model systems for transmembrane pore structures. The most widely accepted model for the anticellular activity of this drug involves the formation of 1:1 Amphotericin/ sterol aggregates which subsequently associate into a transmembrane barrel with a large -OH lined aqueous pore down the middle. The stronger association of Amphotericin with ergosterol versus cholesterol explains the higher toxicity toward fungi. However, conflicting membrane permeability data concerning Amphotericin channel ion selectivity, sterol requirements, and mode of delivery has accumulated over the past fifteen years and suggests there exists a multiplicity of AmB channel structures and modes of action. Some of these mechanisms of action may be even more relevant clinically than the Amphotericin/sterol pore structure. Some of the anticellular membrane damage caused by Amphotericin may be due to formation of membrane defects and non-bilayer phases, channels without sterol or even induction of oxidative damage. In this article we present a survey of recent observations on AmB's activity on model membrane systems. As such, we are mostly concerned with liposome and planar bilayer studies. Some of the newer models explaining AmB s differential effects on cholesterol versus ergosterol containing membranes are presented along with a brief overview of membrane disruption models based on current research on membrane-active amphiphilic peptides. A synthesis and reconciliation of many of these diverse observations is attempted in a model which can accommodate most aspects of the classical sterol/Amphotericin barrel model and more recent observations as well.     

The Time Dependence of Single File Diffusion

The single file diffusion of particles through a narrow pore membrane separating two media is treated as a stochastic birth and death process. A set of differential-difference equations is derived to describe the probability of finding n particles in the pore at any time whose source is the left-hand medium. Explicit time-dependent solutions for an arbitary number of sites are obtained. These can be used to calculate both one-way and net flux as a function of time. Parameters are estimated from steady state permeability data, and the results of some numerical calculations are presented to illustrate the time required to approach a steady state. In many cases, significant time delays can occur.     

Binding of Synapsin I to Synaptic Vesicles: Clues from the Study of its Interactions with Liposomes

Abstract

Synapsin I is a major brain phosphoprotein which interacts with synaptic vesicles and actin in a phosphorylation-dependent fashion. The binding of synapsin I to synaptic vesicles involves interactions with the phospholipid and protein components of the vesicle membrane. The highly hydrophobic NH₂-terminal head region of the protein binds with high-affinity to acidic phospholipids and penetrates the hydrophobic core of the membrane, whereas the basic COOH-terminal tail region does not significantly contribute to this binding. The interaction with phospholipids increases the amount of α-helix in the secondary structure of synapsin I, but does not markedly affect the microenvironment of tryptophan and cysteine residues present in the head region. The results suggest that synapsin I binds to synaptic vesicle phospholipids through amphiphilic and positively charged domains present in its NH2-terminal region and that such an interaction contributes to the high-affinity binding of synapsin I to synaptic vesicles.     

Finite element analysis of biological soft tissue surrounded by a deformable membrane that controls transmembrane flow

Background

Many biological soft tissues are hydrated porous hyperelastic materials, which consist of a complex solid skeleton with fine voids and fluid filling these voids. Mechanical interactions between the solid and the fluid in hydrated porous tissues have been analyzed by finite element methods (FEMs) in which the mixture theory was introduced in various ways. Although most of the tissues are surrounded by deformable membranes that control transmembrane flows, the boundaries of the tissues have been treated as rigid and/or freely permeable in these studies. The purpose of this study was to develop a method for the analysis of hydrated porous hyperelastic tissues surrounded by deformable membranes that control transmembrane flows.

Results

For this, we developed a new nonlinear finite element formulation of the mixture theory, where the nodal unknowns were the pore water pressure and solid displacement. This method allows the control of the fluid flow rate across the membrane using Neumann boundary condition. Using the method, we conducted a compression test of the hydrated porous hyperelastic tissue, which was surrounded by a flaccid impermeable membrane, and a part of the top surface of this tissue was pushed by a platen. The simulation results showed a stress relaxation phenomenon, resulting from the interaction between the elastic deformation of the tissue, pore water pressure gradient, and the movement of fluid. The results also showed that the fluid trapped by the impermeable membrane led to the swelling of the tissue around the platen.

Conclusions

These facts suggest that our new method can be effectively used for the analysis of a large deformation of hydrated porous hyperelastic material surrounded by a deformable membrane that controls transmembrane flow, and further investigations may allow more realistic analyses of the biological soft tissues, such as brain edema, brain trauma, the flow of blood and lymph in capillaries and pitting edema.

     

Characteristics of cross-flow filtration of pullulan broth

Cross-flow filtration of culture broth from Aureobasidium pullulans, which elaborates pullulan, was done with a thin channel-type module and microfiltration membranes made of different materials and with different pore sizes. Various factors affecting the results of the filtration were studied. The specific resistance of the microbial cake was found to be higher than that of bakers yeast, the cells of which are about the same size as an A. pullulans cell, and resistance increased with cultivation time. The flux and transmission of pullulan through the membrane decreased with cultivation time as the specific resistance increased. The flux and transmission ] of pullulan depended on the structure and pore size of the membrane and also on the pH of the broth. With a polysulphone membrane with a nominal pore size of 2.0 m, transmission was nearly 100% with negligible leakage of cells and the flux was high when the pH of the broth was adjusted to 2.0.On leave from Hayashibara Co., Ltd., Amase-minamimachi, Okayama 700 Japan Correspondence to: K. Nakanishi     

Target-organ interaction: Considerations of the effects of sodium and water retaining hormones on renal function

In this paper the characteristics of a membrane having properties similar to those of frog skin are considered in relation to renal function. Such a membrane, as discussed by H. H. Ussing and K. Zerahn (Acta. Physiol. Scand.,23, 110, 1951), is capable of acting as a sodium pump actively transferring sodium ions through the membrane. Water transfer is regarded as dependent upon osmotic and hydrostatic pressures and on the permeability of the membrane to water. It is shown that for a membrane having these properties the rate of transfer of sodium is a function of the rate of transfer of water andvice versa. In this case a change in, say, the flux of water across the membrane may lead to a similarly directed change in the sodium flux across the membrane. If the E.M.F. developed by the sodium pump is controlled by a sodium retaining hormone (SRH.) and the permeability of the membrane to water by antidiuretic hormone (ADH.), it follows that there is an interaction between the two hormones which is a property of the membrane upon which they act. It is suggested that the mechanism of action of the renal tubules with regard to sodium and water excretion may be not entirely dissimilar to that discussed for frog skin, and on this supposition the characteristics of the renal response to certain physiological stimuli are deduced and found to be in excellent agreement with observation. In particular, the excretion of a urine initially hypotonic in response to an isotonic saline infusion is explained as is also the inability of, physiological doses of, ADH to inhibit isotonic or hypertonic saline diuresis. Dr. Cole is in the Department of Medicine, and Mr. Meredith is in the Department of Electrical Engineering.     

Membrane separation of protein precipitates: Studies with cross flow in hollow fibers

Hollow fiber ultrafiltration and microfiltration membranes are examined for the processing of isoelectric soya protein precipitate suspensions. A model based on the various resistances to permeate flux is used to describe membrane performance. The main resistance to permeate flux is due to the interaction between the active membrane and the soluble and precipitated protein; that is, as compared with resistances due to the active membrane itself or the membrane support structure, or arising from concentrated soluble or precipitated protein layers over the membrane surface. Soluble protein rejection and precipitate mean particle diameter are correlated with observed values of this main resistance.In contract to the ultrafiltration of soluble proteins, the flux rates observed when processing protein precipitate suspensions under a similar range of operating conditions do not approach a limiting value with increased transmembrane pressure. At high protein concentrations, greater flux rates may be achieved for precipitated as compared with soluble proteins. The use of a microfiltration membrane does not give further improvement in flux rate; this may be attributed to problems of pore fouling with precipitate particles.