Transport Of Neutral Solutes Research Articles

Confinement effects on distribution and transport of neutral solutes in a small hydrophobic nanopore

Confinement effects on distribution and transport of neutral solutes in a small hydrophobic nanopore

Finite Element Implementation of Computational Fluid Dynamics With Reactive Neutral and Charged Solute Transport in FEBio.

The objective of this study was to implement a novel fluid-solutes solver into the open-source finite element software FEBio, that extended available modeling capabilities for biological fluids and fluid-solute mixtures. Using a reactive mixture framework, this solver accommodates diffusion, convection, chemical reactions, electrical charge effects, and external body forces, without requiring stabilization methods that were deemed necessary in previous computational implementations of the convection-diffusion-reaction equation at high Peclet numbers. Verification and validation problems demonstrated the ability of this solver to produce solutions for Peclet numbers as high as 1011, spanning the range of physiological conditions for convection-dominated solute transport. This outcome was facilitated by the use of a formulation that accommodates realistic values for solvent compressibility, and by expressing the solute mass balance such that it properly captured convective transport by the solvent and produced a natural boundary condition of zero diffusive solute flux at outflow boundaries. Since this numerical scheme was not necessarily foolproof, guidelines were included to achieve better outcomes that minimize or eliminate the potential occurrence of numerical artifacts. The fluid-solutes solver presented in this study represents an important and novel advancement in the modeling capabilities for biomechanics and biophysics as it allows modeling of mechanobiological processes via the incorporation of chemical reactions involving neutral or charged solutes within dynamic fluid flow. The incorporation of charged solutes in a reactive framework represents a significant novelty of this solver. This framework also applies to a broader range of nonbiological applications.

Structural assessment of OsNIP2;1 highlighted critical residues defining solute specificity and functionality of NIP class aquaporins

IntroductionNodulin-26-like intrinsic proteins (NIPs) are integral membrane proteins belonging to the aquaporin family, that facilitate the transport of neutral solutes across the bilayer. The OsNIP2;1 a member of NIP-III class of aquaporins is permeable to beneficial elements like silicon and hazardous arsenic. However, the atomistic cross-talk of these molecules traversing the OsNIP2;1 channel is not well understood. ObjectiveDue to the lack of genomic variation but the availability of high confidence crystal structure, this study aims to highlight structural determinants of metalloid permeation through OsNIP2;1. MethodsThe molecular simulations, combined with site-directed mutagenesis were used to probe the role of specific residues in the metalloid transport activity of OsNIP2;1. ResultsWe drew energetic landscape of OsNIP2;1, for silicic and arsenous acid transport. Potential Mean Force (PMF) construction illuminate three prominent energetic barriers for metalloid passage through the pore. One corresponds to the extracellular molecular entry in the channel, the second located on ar/R filter, and the third size constriction in the cytoplasmic half. Comparative PMF for silicic acid and arsenous acid elucidate a higher barrier for silicic acid at the cytoplasmic constrict resulting in longer residence time for silicon. Furthermore, our simulation studies explained the importance of conserved residues in loop-C and loop-D with a direct effect on pore dynamics and metalloid transport. Next we assessed contribution of predicted key residues for arsenic uptake, by functional complementation in yeast. With the aim of reducing arsenic uptake while maintaining beneficial elements uptake, we identified novel OsNIP2;1 mutants with substantial reduction in arsenic uptake in yeast. ConclusionWe provide a comprehensive assessment of pore lining residues of OsNIP2;1 with respect to metalloid uptake. The findings will expand mechanistic understanding of aquaporin’s metalloid selectivity and facilitate variant interpretation to develop novel alleles with preference for beneficial metalloid species and reducing hazardous ones.

Combined electroosmotic and pressure-driven transport of neutral solutes across a rough, porous-walled microtube.

A number of microfluidic systems of interest essentially consist of micro-scaled channels/tubes, whose walls are inherently rough. The novelty of the current study lies in exploring the impact of the wall roughness on mass transfer in the case of flow through a microtube with porous wall. The current investigation is possibly the first attempt at exploring the effect of mass transfer for a porous-walled, rough microtube, as earlier studies were limited to the analysis of hydrodynamic and thermal effects only in an impervious microtube. In particular, the effects of the corrugation amplitude and the wavenumber on the mass transport have been assessed in detail in this work, via a combination of perturbation approximations and numerical analysis. Several interesting revelations are elicited regarding the effects of these pertinent parameters on the mass transfer coefficient, permeation flux, wall surface concentration, and delivery flux of the neutral solute. It has been unveiled that it is possible to enhance the solute mass flux by 10% via appropriate tuning of corrugation amplitude. The findings of the study can help in better understanding of mass transport for a porous-walled, rough microtube, which has critical relevance in several important applications such as micromixers, targeted drug delivery, and so on.

Permeability and diffusion resistance of porous membranes: Analytical theory and its numerical test.

This study is devoted to the transport of neutral solutes through porous flat membranes, driven by the solute concentration difference in the reservoirs separated by the membrane. Transport occurs through membrane channels, which are assumed to be non-overlapping, identical, straight cylindrical pores connecting the reservoirs. The key quantities characterizing transport are membrane permeability and its diffusion resistance. Such transport problems arising in very different contexts, ranging from plant physiology and cell biology to chemical engineering, have been studied for more than a century. Nevertheless, an expression giving the permeability for a membrane of arbitrary thickness at arbitrary surface densities of the channel openings is still unknown. Here, we fill in the gap and derive such an expression. Since this expression is approximate, we compare its predictions with the permeability obtained from Brownian dynamics simulations and find good agreement between the two.

A high-throughput yeast approach to characterize aquaporin permeabilities: Profiling the Arabidopsis PIP aquaporin sub-family.

Engineering membrane transporters to achieve desired functionality is reliant on availability of experimental data informing structure-function relationships and intelligent design. Plant aquaporin (AQP) isoforms are capable of transporting diverse substrates such as signaling molecules, nutrients, metalloids, and gases, as well as water. AQPs can act as multifunctional channels and their transport function is reliant on many factors, with few studies having assessed transport function of specific isoforms for multiple substrates. High-throughput yeast assays were developed to screen for transport function of plant AQPs, providing a platform for fast data generation and cataloguing of substrate transport profiles. We applied our high-throughput growth-based yeast assays to screen all 13 Arabidopsis PIPs (AtPIPs) for transport of water and several neutral solutes: hydrogen peroxide (H2O2), boric acid (BA), and urea. Sodium (Na+) transport was assessed using elemental analysis techniques. All AtPIPs facilitated water and H2O2 transport, although their growth phenotypes varied, and none were candidates for urea transport. For BA and Na+ transport, AtPIP2;2 and AtPIP2;7 were the top candidates, with yeast expressing these isoforms having the most pronounced toxicity response to BA exposure and accumulating the highest amounts of Na+. Linking putative AtPIP isoform substrate transport profiles with phylogenetics and gene expression data, enabled us to align possible substrate preferences with known and hypothesized biological roles of AtPIPs. This testing framework enables efficient cataloguing of putative transport functionality of diverse AQPs at a scale that can help accelerate our understanding of AQP biology through big data approaches (e.g. association studies). The principles of the individual assays could be further adapted to test additional substrates. Data generated from this framework could inform future testing of AQP physiological roles, and address knowledge gaps in structure-function relationships to improve engineering efforts.

Confinement Effects on Distribution and Transport of Neutral Solutes in a Small Hydrophobic Nanopore.

Molecular dynamics simulations are used to study confinement effects in small cylindrical silica pores with extended hydrophobic surface functionalization as realized, for example, in reversed-phase liquid chromatography (RPLC) columns. In particular, we use a 6 nm cylindrical and a 10 nm slit pore bearing the same C18 stationary phase to compare the conditions inside the smaller-than-average pores within an RPLC column to column-averaged properties. Two small, neutral, apolar to moderately polar solutes are used to assess the consequences of spatial confinement for typical RPLC analytes with water (W)-acetonitrile (ACN) mobile phases at W/ACN ratios between 70/30 and 10/90 (v/v). The simulated data show that true bulk liquid behavior, as observed over an extended center region in the 10 nm slit pore, is not recovered within the 6 nm cylindrical pore. Instead, the ACN-enriched solvent layer around the C18 chain ends (the ACN ditch), a general feature of hydrophobic interfaces equilibrated with aqueous-organic liquids, extends over the entire pore lumen of the small cylindrical pore. This renders the entire pore a highly hydrophobic environment, where, contrary to column-averaged behavior, neither the local nor the pore-averaged sorption and diffusion of analytes scales directly with the W/ACN ratio of the mobile phase. Additionally, the solute polarity-related discrimination between analytes is enhanced. The consequences of local ACN ditch overlap in RPLC columns are reminiscent of ion transport in porous media with charged surfaces, where electrical double-layer overlap occurring locally in smaller pores leads to discrimination between co- and counterionic species.

PIPs from Fragaria vesca: A structural analysis of native and mutated protein

Aquaporins are an ancient family of membrane channel proteins present in all eukaryotes and most prokaryotes, and apart from water, allow the transport of neutral solutes and organic compounds through the pore. These proteins are essential role differentially expressed during ripening in Fragaria vesca fruits. Fv PIP2-1a is intensively expressed in fruits, inclusive several other proteins member are differentially expressed in fruit but also in other plant tissues. Phylogenetic analysis shows that Fv PIP2-1a grouped with other Fragaria proteins and far apart from other F. vesca PIP proteins. A structural model for Fv PIP2-1a protein was built by comparative modelling methodology, which was validated and refined by molecular dynamics simulation. Fv PIP2-1a structure consists of 6 transmembrane regions and two NPA domains. The mobilization of water was analyzed by molecular docking simulations in wildtype and two mutants. Interestingly, the mutant FvPIP2-1a_H214G allowed the prediction of an increment in the flux of water molecules. On contrary, structural analysis predicted that H214E mutation blocked passage of water associated to constriction of the pore.

Reversible and irreversible mitochondrial swelling in vitro

Mitochondrial activity as regards ATP production strongly depends on mitochondrial swelling (MS) mode. Therefore, this work analyzes reversible and irreversible MS using a detailed biophysical model. The reported model includes mechanical properties of the inner mitochondrial membrane (IMM). The model describes MS dynamics for spherically symmetric, axisymmetric ellipsoidal and general ellipsoidal mitochondria. Mechanical stretching properties of the IMM were described by a second-rank rigidity tensor. The tensor components were estimated by fitting to the earlier reported results of in vitro experiments. The IMM rigidity constant of ca. 0.008 dyn/nm was obtained for linear deformations. The model also included membrane bending effects, which were small compared to those of membrane stretching. The model was also tested by simulation of the earlier reported experimental data and of the system dynamics at different initial conditions, predicting the system behavior. The transition criteria from reversible to irreversible swelling were determined and tested.The presently developed model is applicable directly to the analysis of in vitro experimental data, while additional improvements are necessary before it could be used to describe mitochondrial swelling in vivo. The reported theoretical model also provides an idea of physically consistent mechanism for the permeability transport pore (PTP) opening, which depends on the IMM stretching stress. In the current study, this idea is discussed briefly, but a detailed theoretical analysis of these ideas will be performed later.The currently developed model provides new understanding of the detailed MS mechanism and of the conditions for the transition between reversible and irreversible MS modes. On the other hand, the current model provides useful mathematical tools, that may be successfully used in mitochondrial biophysics research, and also in other applications, predicting the behavior of mitochondria in different conditions of the surrounding media in vitro or cellular cyto(sarco)plasm in vivo. These mathematical tools are based on real biophysical processes occurring in mitochondria. Thus, we note a significant progress in the theoretical approach, which may be used in real biological systems, compared to the earlier reported models.Significance of this study derives from inclusion of IMM mechanical properties, which directly impact the reversible and irreversible mitochondrial swelling dynamics. Reversible swelling corresponds to reversible IMM deformations, while irreversible swelling corresponds to irreversible deformations, with eventual membrane disruption. The IMM mechanical properties are directly dependent on the membrane biochemical composition and structure. The IMM deformationas are induced by osmotic pressure created by the ionic/neutral solute imbalance between the mitochondrial matrix media and the bulk solution in vitro, or cyto(sarco)plasm in vivo.The novelty of the reported model is in the biophysical mechanism detailing ionic and neutral solute transport for a large number of solutes, which were not taken into account in the earlier reported biophysical models of MS. Therefore, the reported model allows understanding response of mitochondria to the changes of initial concentration(s) of any of the solute(s) included in the model. Note that the values of all of the model parameters and kinetic constants have been estimated and the resulting complete model may be used for quantitative analysis of mitochondrial swelling dynamics in conditions of real in vitro experiments.

Voltage-Dependent Transport of Neutral Solutes through Nanopores: A Molecular View.

The permeation of (neutral) molecules through nanopores in the presence of external voltages depends on several factors including pore electrostatics, electrophoretic force, and electro-osmotic drag. In earlier single-channel electrophysiology experiments, voltage-dependent asymmetric transport of neutral α-cyclodextrin (α-CD) molecules through the biological nanopore ΔCymA was observed. The voltage-dependent ion-associated flow of water, the so-called electro-osmotic flow, has been suggested to be the key factor behind the observed asymmetric behavior. The influence of pore electrostatics and electrophoretic force and their interplay with the electro-osmotic drag with varying buffers and voltages has not yet been analyzed at the molecular level. Hence, the detailed physical mechanism behind this intriguing permeation process is in part still unclear. In the present study, we have performed 36 μs all-atom free energy calculations by combining applied-field molecular dynamics simulations with metadynamics techniques. The influence of several ionic conditions as well as external voltages on the permeation of α-CD molecules across the ΔCymA pore has been investigated. To decipher the thermodynamic and kinetic details, the lowest energy paths and the permeation times for α-CD translocation have been estimated. In the presence of KCl or MgCl2 salts, the charge of the cations is found to control the direction and magnitude of the electro-osmotic flow, which in turn strongly affects α-CD permeation. Overall, the present findings significantly improve the fundamental understanding of the voltage-dependent transport of neutral solutes across nanopores.

Effects of finite ion size on transport of neutral solute across porous wall of a nanotube

Effect of finite ion size on the transport of a neutral solute across the porous wall of a nanotube is presented in this study. Modified Poisson–Boltzmann equation without the Debye–Huckel approximation is used to determine the potential distribution within the tube. Power law fluid is selected for the study, as its rheology resembles closely to the real-life physiological fluids. The flow within the tube is actuated by the combined effects of pressure and electroosmotic forces. Steady-state solute balance equation is solved by the similarity technique in order to track the solute transport across the tube. The effects of ionic radius, ionic concentration, and flow behavioral index on the length-averaged Sherwood number, permeate flux, and permeate concentration are analyzed. This study will be extremely helpful in predicting the transport characteristics of a neutral solute in real physiological systems and also to fine-tune the performance of microfluidic devices having porous wall.

Application of the Brown dynamics fluctuation-dissipation theorem to the study of Plasmodium berghei transporter protein PbAQP.

In this article, the Brownian dynamics fluctuation-dissipation theorem (BD-FDT) is applied to the study of transport of neutral solutes across the cellular membrane of Plasmodium berghei (Pb), a disease-causing parasite. Pb infects rodents and causes symptoms in laboratory mice that are comparable to human malaria caused by Plasmodium falciparum (Pf). Due to the relative ease of its genetic engineering, P. berghei has been exploited as a model organism for the study of human malaria. P. berghei expresses one type of aquaporin (AQP), PbAQP, and, in parallel, P. falciparum expresses PfAQP. Either PbAQP or PfAQP is a multifunctional channel protein in the plasma membrane of the rodent/human malarial parasite for homeostasis of water, uptake of glycerol, and excretion of some metabolic wastes across the cell membrane. This FDT-study of the channel protein PbAQP is to elucidate how and how strongly it interacts with water, glycerol, and erythritol. It is found that erythritol, which binds deep inside the conducting pore of PbAQP/PfAQP, inhibits the channel protein's functions of conducting water, glycerol etc. This points to the possibility that erythritol, a sugar substitute, may inhibit the malarial parasites in rodents and in humans.

Transport of Neutral and Charged Solutes in Imidazolium-Functionalized Poly(phenylene oxide) Membranes for Artificial Photosynthesis

Anion exchange membranes (AEMs) play an essential role in artificial photosynthesis devices, which photoelectrochemically convert CO2 and water into useful products. AEMs allow the transport of cha...

Effect of electrolyte nature in mass transport of a neutral solute in a microtube with porous wall

AbstractElectroosmotic flow in a microchannel is an active area in microfluidics. Microchannels with porous wall are advantageous due to selective separation and enhanced mass transport. An economic and innovative method to fabricate hollow microtubes and their application in electrokinetics are illustrated. Effects of asymmetric electrolyte on mass transport of a neutral macrosolute in the microtube with porous wall are investigated. The combined velocity profile including both pressure‐driven and electroosmotic flow is modeled for different electrolytes. It is found from the study that the addition of higher valency asymmetric electrolyte (3:1) increases transport of neutral solutes across the porous wall compared to its symmetric counterpart (1:1). The developed model was validated with the experimental results, using a cartridge having hollow microtubes with porous wall. This study would be helpful to select an appropriate electrolyte, improving the design, and performance prediction of microfluidic devices.

Transport of neutral solutes in a viscoelastic solvent through a porous microchannel

We study the effect of viscoelasticity on the transportation of neutral solutes through a porous microchannel. The underlying transport phenomenon, modelled using the simplified Phan-Thien-Tanner constitutive equation, is actuated by the combined influence of pressure gradient and electroosmosis. Here, we obtain the closed form solution for the velocity distribution inside the flow domain and calculate the concentration profiles of the neutral solutes within the mass transport boundary layer by invoking the similarity solution approach. To establish the efficacy of viscoelastic solvents in the transportation of neutral solutes, which may find relevance in transdermal drug delivery applications, here we show the variations in the local solute concentration, the length averaged solute concentration at the wall, and the Sherwood number with the viscoelastic parameter. The present study infers that the shear-thinning nature of the viscoelastic fluid enhances the convective mass transfer as well as the permeation rate in the porous membranes. A complex interplay between the fluid rheology and the porous structure of the walls influenced by the electrochemistry at the interfacial scale modulates the mass transfer boundary layer of neutral solutes, implicating an effective method of mass transport in transdermal drug delivery applications.

Molecular insights into the plasma membrane intrinsic proteins roles for abiotic stress and metalloids tolerance and transport in plants

Aquaporins are channel proteins reported to play multiple functions in plants ranging from water, solutes, metalloids (arsenic, boron, silicon) transport, and tolerance to abiotic stresses including drought, salinity and cold. Based on their localization and sequence similarities, aquaporins have been classified into seven major subfamilies: plasma membrane intrinsic proteins (PIPs), nodulin 26-like intrinsic proteins, tonoplast intrinsic proteins, small basic intrinsic proteins, GlpF-like intrinsic protein, hybrid intrinsic proteins and the uncategorized (X) intrinsic proteins. PIP subfamily is one of the biggest subfamilies of aquaporin superfamily and they are localized to plasma membrane. Members of PIPs are involved in water and small neutral solute transport and play an important role in maintaining water homeostasis under environmental stress and are known to provide tolerance to various abiotic stresses. Recently, members of PIP subfamily have been shown to be involved in the bidirectional transport of metalloids, arsenic and boron in plants. This review highlights the involvement of various PIP homologs in plant stress responses against a variety of environmental stresses and metalloid transport and tolerance. Molecular insights and biotechnological approaches for developing climate resilient crops by modulating PIPs will be discussed.

Transport of small and neutral solutes through reverse osmosis membranes: Role of skin layer conformation of the polyamide film

The polyamide skin layer of reverse osmosis (RO) membranes was characterised using advanced and complementary analytical techniques to investigate the mechanisms underlying the permeation of contaminants of emerging concern in potable water reuse – N-nitrosodimethylamine (NDMA) and N-nitrosomethylethylamine (NMEA). This study used five RO membrane samples with similar membrane properties. The five RO membrane samples spanned over a large range of water permeance (0.9–5.8 L/m2 h bar) as well as permeation of NDMA (9–66%) and NMEA (3–29%). Despite these differences among the five RO membranes, characterisations of the skin layer using positron annihilation lifetime spectroscopy, atomic force microscopy and field emission scanning electron microscopy revealed almost no variation in their free-volume hole-radius (0.270–0.275 nm), effective surface area (198–212%) and thickness (30–35 nm) of the skin layer. The results suggest that there could be other RO skin layer properties, such as the interconnectivity of the protuberances within the polyamide skin layer additional to the free-volume hole-size and thickness of the skin layer, which can also govern water and solute permeation.

Tamarix hispida aquaporin ThPIP2;5 confers salt and osmotic stress tolerance to transgenic Tamarix and Arabidopsis

Aquaporin (AQP) proteins constitute a large family of protein channels that facilitate the transport of water and small neutral solutes through biological membranes, which is important for plants to combat abiotic stress. However, the precise functions of AQP genes involved in abiotic stress are not completely understood in plants. In this study, ThPIP2;5, an AQP gene of the PIP2 subgroup, was cloned and characterized from Tamarix hispida. Cellular localization assays showed that ThPIP2;5 was localized to the plasma membrane. Transgenic Arabidopsis plants overexpressing ThPIP2;5 displayed improved seed germination rates and increased root growth and fresh weight gain under salt and osmotic stresses, indicating that ThPIP2;5 can improve abiotic stress tolerance. ThPIP2;5-overexpressing and RNAi-silencing T. hispida plants were generated using the transient transformation method and selected for gain- and loss-of ThPIP2;5 analyses, respectively. Overexpression of ThPIP2;5 in transgenic Tamarix and Arabidopsis plants increased ROS-scavenging capability, activities of antioxidant enzymes and proline contents; decreased malondialdehyde (MDA) and H2O2 contents; and reduced electrolyte leakage rates compared to equivalent controls under salt and osmotic stresses. Together, these data suggested that ThPIP2;5 plays an important physiological role in abiotic stress tolerance in transgenic plants by reducing ROS accumulation and membrane damage and increasing the activities of antioxidants.

An Experimental and Finite Element Protocol to Investigate the Transport of Neutral and Charged Solutes across Articular Cartilage

An Experimental and Finite Element Protocol to Investigate the Transport of Neutral and Charged Solutes across Articular Cartilage

An Experimental and Finite Element Protocol to Investigate the Transport of Neutral and Charged Solutes across Articular Cartilage.

Osteoarthritis (OA) is a debilitating disease that is associated with degeneration of articular cartilage and subchondral bone. Degeneration of articular cartilage impairs its load-bearing function substantially as it experiences tremendous chemical degradation, i.e. proteoglycan loss and collagen fibril disruption. One promising way to investigate chemical damage mechanisms during OA is to expose the cartilage specimens to an external solute and monitor the diffusion of the molecules. The degree of cartilage damage (i.e. concentration and configuration of essential macromolecules) is associated with collisional energy loss of external solutes while moving across articular cartilage creates different diffusion characteristics compared to healthy cartilage. In this study, we introduce a protocol, which consists of several steps and is based on previously developed experimental micro-Computed Tomography (micro-CT) and finite element modeling. The transport of charged and uncharged iodinated molecules is first recorded using micro-CT, which is followed by applying biphasic-solute and multiphasic finite element models to obtain diffusion coefficients and fixed charge densities across cartilage zones.