Membrane Geometry Research Articles

Weaker neuroligin 2 - neurexin 1β interaction tethers membranes and signal synaptogenesis through clustering.

Single-pass transmembrane proteins neuroligin (NL) and neurexin (NRX) constitute a pair of synaptic adhesion molecules (SAMs) that are essential for the formation of functional synapses. Binding affinities vary by ∼ 1000 folds between arrays of NL and NRX subtypes, which contribute to chemical and spatial specificities. Current structures are obtained with truncated extracellular domains of NL and NRX and are limited to the higher-affinity NL1/4-NRX complexes. How NL-NRX interaction leads to functional synapses remains unknown. Here we report structures of full-length NL2 alone, and in complex with NRX1β in several conformations, which has the lowest affinity among major NL-NRX subtypes. We show how conformational flexibilities may help in adapting local membrane geometry, and reveal mechanisms underlying variations in NL-NRX affinities modulation. We further show that, despite lower affinity, NL2-NRX1β interaction alone is capable of tethering different lipid membranes in total reconstitution, and that NL2 and NRX1β cluster at inter-cellular junctions without the need of other synaptic components. In addition, NL2 combines with the master post-synaptic scaffolding protein gephyrin and clusters neurotransmitter receptors at cellular membrane. These findings suggest dual roles of NL2 - NRX1β interaction - both as mechanical tether, and as signaling receptors, to ensure correct spatial and chemical coordination between two cells to generate function synapses.

Deformation and enclosed volume change of axisymmetric non-linear dielectric elastomer membrane pump: a theoretical study

Abstract This work investigates the change in the enclosed volume of an axisymmetric non-linear hyper-elastic membrane pump subjected to dielectric actuation. The equilibrium equations in cylindrical coordinates, coupled with non-linear constitutive relations, are solved numerically to obtain the deformed membrane geometry under pressure loading (using Variational Calculus). The effect of dielectric actuation is then incorporated by considering the change in material properties and deformation induced by the applied electric field. The deformed geometry under dielectric actuation is determined, and the change in enclosed volume is calculated by comparing the deformed states with and without the applied electric field. The proposed approach enables quantifying the volumetric change in non-linear hyper-elastic membrane pumps due to dielectric actuation for potential applications in soft robotics, adaptive optics, and microfluidics. By non-dimensionalizing variables, key dimensionless parameters governing the problem are identified for broader applicability. Furthermore, this methodology can estimate volume changes for different electric actuations when a specific material is chosen with experimentally derived parameter trends, facilitating material selection or synthesis to meet targeted volumetric requirements.

Membrane curvature sensing and symmetry breaking of the M2 proton channel from Influenza A.

The M2 proton channel aids in the exit of mature influenza viral particles from the host plasma membrane through its ability to stabilize regions of high negative Gaussian curvature (NGC) that occur at the neck of budding virions. The channels are homo-tetramers that contain a cytoplasm-facing amphipathic helix (AH) that is necessary and sufficient for NGC generation; however, constructs containing the transmembrane spanning helix, which facilitates tetramerization, exhibit enhanced curvature generation. Here, we used all-atom molecular dynamics (MD) simulations to explore the conformational dynamics of M2 channels in lipid bilayers revealing that the AH is dynamic, quickly breaking the fourfold symmetry observed in most structures. Next, we carried out MD simulations with the protein restrained in four- and twofold symmetric conformations to determine the impact on the membrane shape. While each pattern was distinct, all configurations induced pronounced curvature in the outer leaflet, while conversely, the inner leaflets showed minimal curvature and significant lipid tilt around the AHs. The MD-generated profiles at the protein-membrane interface were then extracted and used as boundary conditions in a continuum elastic membrane model to calculate the membrane-bending energy of each conformation embedded in different membrane surfaces characteristic of a budding virus. The calculations show that all three M2 conformations are stabilized in inward-budding, concave spherical caps and destabilized in outward-budding, convex spherical caps, the latter reminiscent of a budding virus. One of the C2-broken symmetry conformations is stabilized by 4 kT in NGC surfaces with the minimum energy conformation occurring at a curvature corresponding to 33 nm radii. In total, our work provides atomistic insight into the curvature sensing capabilities of M2 channels and how enrichment in the nascent viral particle depends on protein shape and membrane geometry.

Synthesis of geometrically realistic and watertight neuronal ultrastructure manifolds for in silico modeling.

Understanding the intracellular dynamics of brain cells entails performing three-dimensional molecular simulations incorporating ultrastructural models that can capture cellular membrane geometries at nanometer scales. While there is an abundance of neuronal morphologies available online, e.g. from NeuroMorpho.Org, converting those fairly abstract point-and-diameter representations into geometrically realistic and simulation-ready, i.e. watertight, manifolds is challenging. Many neuronal mesh reconstruction methods have been proposed; however, their resulting meshes are either biologically unplausible or non-watertight. We present an effective and unconditionally robust method capable of generating geometrically realistic and watertight surface manifolds of spiny cortical neurons from their morphological descriptions. The robustness of our method is assessed based on a mixed dataset of cortical neurons with a wide variety of morphological classes. The implementation is seamlessly extended and applied to synthetic astrocytic morphologies that are also plausibly biological in detail. Resulting meshes are ultimately used to create volumetric meshes with tetrahedral domains to perform scalable in silico reaction-diffusion simulations for revealing cellular structure-function relationships. Availability and implementation: Our method is implemented in NeuroMorphoVis, a neuroscience-specific open source Blender add-on, making it freely accessible for neuroscience researchers.

β-galactosidase immobilization on ceramic ultrafiltration membrane for simultaneous lactose hydrolysis and protein separation

Protein and lactose of cheese whey can be separated using ultrafiltration membranes and lactose can be hydrolyzed by β-galactosidase. This study investigated the integration of ultrafiltration and enzymatic hydrolysis for simultaneous protein concentration and lactose hydrolysis. β-galactosidase was immobilized on ceramic membrane via surface activation with gelatin and subsequent enzyme cross-linking with glutaraldehyde. Membrane geometries, buffer types, gelatin and enzyme concentrations were optimized. The optimal results yielded a 63 % enzyme immobilization efficiency and a 93 % lactose hydrolysis rate by using disc membrane, sodium acetate buffer (pH 4.8), sodium phosphate buffer (pH 7.5), 0.1 g/L gelatin concentration, and 5.0 g/L enzyme concentration. The optimized enzymatic membrane was evaluated with synthetic and real whey. In synthetic whey, 85 % lactose hydrolysis and 89 % protein rejection were achieved. While in real whey, 72 % lactose hydrolysis and 83 % protein recovery were obtained. This approach offers a single-step, efficient, and scalable method for whey valorization with potential for industrial applications.

Analyzing Lipid Membrane Defects via a Coarse-Grained to Triangulated Surface Map: The Role of Lipid Order and Local Curvature in Molecular Binding.

Lipid packing defects are known to serve as quantitative indicators for protein binding to lipid membranes. This paper presents a protocol for mapping molecular lipid detail onto a triangulated continuum leaflet representation. Besides establishing the desired forward counterpart to the existing inverse TS2CG map, this coarse-grained to triangulated surface (CG2TS) map enables straightforward extraction of the defect characteristics for any membrane geometry found in nature. We have applied our protocol to investigate the role of local curvature and varying lipid packing on the defect constant π. We find that the defect size is greatly influenced by both factors, arguing strongly against the usual assignment of a single defect constant in the case of more realistic membrane conditions. An important discovery is that lipids in the gel phase produce larger defects, or a higher π, in domains of high (local) curvature than the same lipid in a liquid phase of any curvature. This finding suggests that membranes featuring very ordered lipid packing can bind proteins via large defects in curved regions. Finally, we propose a route for estimating defect constants directly from the standard membrane properties. Identifying the precise role of composition, lipid (tail) order, and (local) curvature in defects for the irregular lipid structures that are (temporally) present in many biological processes is instrumental for obtaining fundamental insight as well as for a rational design of membrane binding targets.

Diffusion Analyses along Mean and Gaussian-Curved Membranes with CurD.

Curved cellular membranes are both abundant and functionally relevant. While novel tomography approaches reveal the structural details of curved membranes, their dynamics pose an experimental challenge. Curvature especially affects the diffusion of lipids and macromolecules, yet neither experiments nor continuum models distinguish geometric effects from those caused by curvature-induced changes in membrane properties. Molecular simulations could excel here, yet despite community interest toward curved membranes, tools for their analysis are still lacking. Here, we satisfy this demand by introducing CurD, our novel and openly available implementation of the Vertex-oriented Triangle Propagation algorithm to the study of lipid diffusion along membranes with mean and/or Gaussian curvature. This approach, aided by our highly optimized implementation, computes geodetic distances significantly faster than conventional implementations of path-finding algorithms. Our tool, applied to coarse-grained simulations, allows for the first time the analysis of curvature effects on diffusion at size scales relevant to physiological processes such as endocytosis. Our analyses with different membrane geometries reveal that Gaussian curvature plays a surprisingly small role on lipid motion, whereas mean curvature; i.e., the packing of lipid headgroups largely dictates their mobility.

The acoustics of absorbers comprising a flexible perforated membrane backed by a stack of granular material

It has been found that when a layer of activated carbon partially fills the space behind a finite, edge-constrained, tensioned impermeable membrane, the absorption peaks due to the modal response of the membrane can be significantly enhanced in the low frequency range. In the present work, the modeling aspects of the latter work have been extended to allow the membrane to be both tensioned and flexurally stiff, and furthermore, to be micro-perforated, thus expanding the treatment design space. Second, the particle layer behind the membrane is modeled by using a two-dimensional finite difference implementation of the Biot poro-elastic theory which then accounts for the interaction of the particle layer and walls that contain it: i.e., the solid phase of the particle stack itself is allowed to exhibit modal behavior in the radial direction. The interaction of the membrane nearfield and the particle stack, which creates a nearfield damping effect, is also fully captured. Finally, the model accounts for the hierarchical porosity of activated carbon. The model has been verified by comparison with measurements and it has been found that strikingly high levels of low frequency absorption can be realized by appropriate optimization of the membrane and particle stack properties and geometry.

Electrokinetic index: A new metric for advanced characterization of membranes with various geometries

Electrokinetic measurements to determine the electrical properties (zeta potential) of membrane surfaces have become increasingly popular in the toolbox of characterization techniques. However, it has been established in the literature that parasitic phenomena such as electrokinetic leakage can hamper data interpretation, leading to not only quantitative but also qualitative errors in membrane zeta potential determination. To date, the only method for highlighting and accounting for electrokinetic leakage is limited to flat-sheet membranes. In this letter, we propose an alternative method that is much less time-consuming and applicable to all membrane geometries. This method is based on the determination of the electrokinetic index, which we define as the ratio of the apparent zeta potentials determined from single measurements of the streaming current and streaming potential coefficients. We show that variation in the electrokinetic index reflects modifications occurring within the membrane matrix (in addition to surface properties alteration). The chemical degradation of polyethersulfone (PES)-based flat-sheet and hollow-fiber membranes is used as a proof of concept, but the proposed approach is readily transposable to other problems of practical interest, such as e.g. membrane fouling. This work also paves the way for the development of a new type of electrokinetic sensors for on-line monitoring of membrane operations.

Modeling membrane geometries implicitly in Rosetta.

Interactions between membrane proteins (MPs) and lipid bilayers are critical for many cellular functions. In the Rosetta molecular modeling suite, the implicit membrane energy function is based on a "slab" model, which represent the membrane as a flat bilayer. However, in nature membranes often have a curvature that is important for function and/or stability. Even more prevalent, in structural biology research MPs are reconstituted in model membrane systems such as micelles, bicelles, nanodiscs, or liposomes. Thus, we have modified the existing membrane energy potentials within the RosettaMP framework to allow users to model MPs in different membrane geometries. We show that these modifications can be utilized in core applications within Rosetta such as structure refinement, protein-protein docking, and protein design. For MP structures found in curved membranes, refining these structures in curved, implicit membranes produces higher quality models with structures closer to experimentally determined structures. For MP systems embedded in multiple membranes, representing both membranes results in more favorable scores compared to only representing one of the membranes. Modeling MPs in geometries mimicking the membrane model system used in structure determination can improve model quality and model discrimination.

Multi-objective optimization of a forward osmosis process for desalination using a non-dominated sorting genetic algorithm

Forward osmosis optimization has been typically focused on enhancing the water flux or reducing the cost. This paper suggests a methodology to optimize the technical and economic performance simultaneously for brackish water desalination using MgCl2 draw solution. FO models as well as economic equations were developed within DWSIM software and validated using experimental data from the literature. Sensitivity analysis revealed a trade-off between water flux and the levelized cost of water; design parameters such as membrane geometry and module channels, and operating conditions, especially mass flowrates of the solutions and DS molarity showed opposing effects on the two aforementioned key design parameters. Consequently, the formulated optimization problem involves two conflicting objective functions and several decision variables and constraints. To address this challenge, an optimization routine was developed using the non-dominated sorting genetic algorithm (NSGA-II), DWSIM, and Python. Additionally, the key NSGA-II hyperparameters were assessed in order to obtain a satisfactory global Pareto front. The optimal design requires 37 FO modules in series each with 44 channels, while the optimal BW and DS flowrates are 3.463 and 2.467 kg/s, respectively. The optimal configuration is utilized successfully to design three FO units of different water production capacities.

A high-order sharp-interface immersed boundary solver for high-speed flows

A sharp-interface immersed boundary (IB) solver for the three-dimensional compressible Navier-Stokes equations with shock discontinuities is presented. The IB method is based on high-order schemes and a ghost-cell method which uses Taylor polynomial interpolation and weighted least-squares error minimization to impose the boundary conditions on the immersed boundary. The results show that the method enables robust and accurate calculation of high-speed flow problems involving complex geometries, moving boundaries, and solid and membrane geometries. Third-order accuracy or higher is maintained even for supersonic conditions. The numerical framework is validated through several two-dimensional and three-dimensional benchmark problems at subsonic and supersonic speeds. Additionally, the method is demonstrated for airfoil dynamic stall and wing-store interaction investigations.

Flow control by circular cavities in lateral flow porous membranes.

This research explores the flow penetration in porous media by virtue of capillary action and geometric control of the liquid imbibition rate in microfluidic paper-based analytical devices (μPADs) having applications in food quality management, medical diagnostics, and environmental monitoring. We examine changes in flow resistance and membrane geometry, aiming to understand factors influencing capillary penetration rates for various practical applications. We conducted experiments and simulations using lateral porous membranes and altered the flow resistance by changing the liquids or the paper channel geometry by adding cavities. From experiments, it was revealed that by creating a circular cavity in the paper channel, the penetration rate was sufficiently altered. Moreover, increasing the cavity size and type of liquid (w.r.t. viscosity) also caused a decrease in the flow rate. Imbibition rates were also influenced by the position of the cavities in the paper channel. The maximum delay for water was almost 2 times with a 16 mm circular cavity located at 3 cm from strip bottom edge. Overall, we attained a maximum delay in the case of castor oil which was almost 85 times slower than water and 3.7 times slower than olive oil. A good agreement was observed with CFD analysis. We believe that this research would help in developing advance techniques to enhance the flow control strategies in μPADs and indicators.

Quantification of membrane geometry and protein sorting on cell membrane protrusions using fluorescence microscopy.

Plasma membranes are flexible and can exhibit numerous shapes below the optical diffraction limit. The shape of cell periphery can either induce or be a product of local protein density changes, encoding numerous cellular functions. However, quantifying membrane curvature and the ensuing sorting of proteins in live cells remains technically demanding. Here, we demonstrate the use of simple widefield fluorescence microscopy to study the geometrical properties (i.e., radius, length, and number) of thin membrane protrusions. Importantly, the quantification of protrusion radius establishes a platform for studying the curvature preferences of membrane proteins.

Lipid membranes supported by polydimethylsiloxane substrates with designed geometry.

The membrane curvature of cells and intracellular compartments continuously adapts to enable cells to perform vital functions, from cell division to signal trafficking. Understanding how membrane geometry affects these processes in vivo is challenging because of the biochemical and geometrical complexity as well as the short time and small length scales involved in cellular processes. By contrast, in vitro model membranes with engineered curvature would provide a versatile platform for this investigation and applications to biosensing and biocomputing. Here, we present a strategy that allows fabrication of lipid membranes with designed shape by combining 3D micro-printing and replica-molding lithography with polydimethylsiloxane to create curved micrometer-sized scaffolds with virtually any geometry. The resulting supported lipid membranes are homogeneous and fluid. We demonstrate the versatility of the system by fabricating structures of interesting combinations of mean and Gaussian curvature. We study the lateral phase separation and how local curvature influences the effective diffusion coefficient. Overall, we offer a bio-compatible platform for understanding curvature-dependent cellular processes and developing programmable bio-interfaces for living cells and nanostructures.

Plasma membrane nanodeformations promote actin polymerization through CIP4/CDC42 recruitment and regulate type II IFN signaling

In their environment, cells must cope with mechanical stresses constantly. Among these, nanoscale deformations of plasma membrane induced by substrate nanotopography are now largely accepted as a biophysical stimulus influencing cell behavior and function. However, the mechanotransduction cascades involved and their precise molecular effects on cellular physiology are still poorly understood. Here, using homemade fluorescent nanostructured cell culture surfaces, we explored the role of Bin/Amphiphysin/Rvs (BAR) domain proteins as mechanosensors of plasma membrane geometry. Our data reveal that distinct subsets of BAR proteins bind to plasma membrane deformations in a membrane curvature radius–dependent manner. Furthermore, we show that membrane curvature promotes the formation of dynamic actin structures mediated by the Rho GTPase CDC42, the F-BAR protein CIP4, and the presence of PI(4,5)P 2 . In addition, these actin-enriched nanodomains can serve as platforms to regulate receptor signaling as they appear to contain interferon-γ receptor (IFNγ-R) and to lead to the partial inhibition of IFNγ-induced JAK/STAT signaling.

Simulation and Analysis of Anodized Aluminum Oxide Membrane Degradation.

Microelectromechanical systems (MEMS)-based filter with microchannels enables the removal of various microorganisms, including viruses and bacteria, from fluids. Membranes with porous channels can be used as filtration interfaces in MEMS hemofilters or mini-dialyzers. The main problems associated with the filtration process are optimization of membrane geometry and fouling. A nanoporous aluminum oxide membrane was fabricated using an optimized two-step anodization process. Computational strength modeling and analysis of the membrane with specified parameters were performed using the ANSYS structural module. A fuzzy simulation was performed for the numerical analysis of flux through the membrane. The membrane was then incorporated with the prototype for successive filtration. The fluid flux and permeation analysis of the filtration process have been studied. Scanning electron microscope (SEM) micrographs of membranes have been obtained before and after the filtration cycles. The SEM results indicate membrane fouling after multiple cycles, and thus the flux is affected. This type of fabricated membrane and setup are suitable for the separation and purification of various fluids. However, after several filtration cycles, the membrane was degraded. It requires a prolonged chemical cleaning. High-density water has been used for filtration purposes, so this MEMS-based filter can also be used as a mini-dialyzer and hemofilter in various applications for filtration. Such a demonstration also opens up a new strategy for maximizing filtration efficiency and reducing energy costs for the filtration process by using a layered membrane setup.

Investigating the effect of C3N membrane geometry on the separation and selectivity of gases

Sour gas includes acidic gases such as hydrogen sulfide and carbon dioxide, which lead to a specific smell, toxicity effect, and a reduction in the overall energy of the gas. In addition, the proximity of these acid gases with water causes the production of a very corrosive acid compound, which increases the price of its transportation. Today, membrane technology is widely used in the separation process due to less energy consumption, low weight and volume, ease of access, as well as the high flexibility of the process. In this research, molecular dynamics simulation of CO2/CH4 separation by modified graphene membrane (C3N) was investigated. First, problem different cavities with different geometrical shapes investigated. By increasing the hole size, regardless of the type of the hole, the efficiency of gas passage increases and reaches a constant value for the size of the holes greater than 3.5 Å. Therefore, increasing the hole size by more than 3.5 Å does not affect the efficiency of the gas passage. Meanwhile, for the size of the holes greater than 2.75 Å, the selectivity between gases reaches zero. Therefore, this hole size is an optimal value. Furthermore, a 4.9 Å hole led to high selectivity (infinity) for carbon dioxide flux of 365.65 (mol/m2.s) that means no methane molecules passed through it.

Semi-Analytical Analysis of a Rigid Rotor Mounted on Four-Pad Hydrostatic Squeeze Film Damper with Single-Action Membrane-Type Restrictors

Abstract The current study is a semi-analytical analysis of the vibratory behaviour of a rigid vertical rotor, supported by a new hydrostatic squeeze film damper (HSFD), consisting of four hydrostatic pads fed through four single-action membrane-type variable-flow restrictors. The Reynolds equation based on the Newtonian theory of lubrication is used and then adapted to our work, which is solved semi-analytically. In this paper, we study the effect of different parameters, the eccentricity, membrane geometry coefficient, pressure ratio and rotational speed, on the main characteristics of a four-pad HSFD. From the simulation results, we observed that at the critical speed, the rigid rotor fed by membrane restrictor shows a decrease in transmitted forces, a decrease in vibration response and good system stability as compared with a similar rotor fed by capillary restrictor. From the results reported in this work, we observed good agreement between our study and other works.

Performance evaluation and optimization of hollow fiber membrane contactors for carbon dioxide absorption: A comparative study of ammonia, ethanolamine, and diethanolamine solvents

Membrane absorption is an emerging technology that amalgamates the merits of chemical absorption and membrane separation. However, the pivotal choice of solvent profoundly influences the overall performance of the membrane contactor. In this paper, a robust two-dimensional (2D) steady-state non-wetting mathematical and physical model of a hollow fiber membrane contactor (HFMC) was established. COMSOL software was used to solve the model equation of the membrane contactor. The impacts of ammonia, ethanolamine (MEA) and diethanolamine (DEA) on carbon dioxide absorption under different operating conditions and membrane geometry properties were simulated and compared. Results showed that the utilization of NH3 as the solvent in HFMC showcases performance akin to that of MEA, a substantial advantage over DEA. Notably, the performance disparity between ammonia and MEA might alter significantly in response to varying operating parameters. For instance, the CO2 removal performance of HFMC using aqueous ammonia surpasses that of MEA when the CO2 volume fraction exceeds 19 %. Moreover, hollow fibers featuring larger inner diameters and lengths endow a heightened effective mass-transfer area, thereby facilitating superior carbon dioxide removal performance.