Membrane Boundary Research Articles

Numerical Simulation Study on Relationship between the Fracture Mechanisms and Residual Membrane Stresses of Metallic Material.

The distribution and dissipation energies in fracture mechanisms were a critical challenge to derive, especially for this ultra-thin sample. The membrane failure, which is the end of the fracture mechanisms, is a result of the cone wave reflections from the backend membrane boundaries. These reflections delay the failure processes due to the shock impacts. To compare these results with the experimental work, a numerical simulation was conducted for these processes. The cylinder-shaped rigid projectile was impacted using a frictionless Lagrange solver. The target was a cartridge brass circle plate clamped at its perimeter, and its zone was refined to a ten-times higher meshing density for better analysis. The erosion and cut-off controls involved a zero-gap interaction condition and an instantaneous geometric erosion strain of 200%. Due to the maximum projectile velocity of 382 m/s having the slowest perforation, the target thickness was found to be 5.5 mm. The fracture mechanism phenomena, such as tensile, compressive, through-thickness, and growth in-plane delamination, propagating delamination, and local punch shear waves were observed. After deducting tensile and flexural strengths from the last experiment, a total residual membrane stress of 650 MPa was found. This result indicated a relationship between the fracture mechanisms and residual membrane stresses of metallic material.

Application of Rapid Fluorescence Lifetime Imaging Microscopy (RapidFLIM) to Examine Dynamics of Nanoparticle Uptake in Live Cells.

A key challenge in nanomedicine stems from the continued need for a systematic understanding of the delivery of nanoparticles in live cells. Complexities in delivery are often influenced by the biophysical characteristics of nanoparticles, where even subtle changes to nanoparticle designs can alter cellular uptake, transport and activity. Close examination of these processes, especially with imaging, offers important insights that can aid in future nanoparticle design or translation. Rapid fluorescence lifetime imaging microscopy (RapidFLIM) is a potentially valuable technology for examining intracellular mechanisms of nanoparticle delivery by directly correlating visual data with changes in the biological environment. To date, applications for this technology in nanoparticle research have not been explored. A PicoQuant RapidFLIM system was used together with commercial silica nanoparticles to follow particle uptake in glioblastoma cells. Importantly, RapidFLIM imaging showed significantly improved image acquisition speeds over traditional FLIM, which enabled the tracking of nanoparticle uptake into subcellular compartments. We determined mean lifetime changes and used this to delineate significant changes in nanoparticle lifetimes (>0.39 ns), which showed clustering of these tracks proximal to both extracellular and nuclear membrane boundaries. These findings demonstrate the ability of RapidFLIM to track, localize and quantify changes in single nanoparticle fluorescence lifetimes and highlight RapidFLIM as a valuable tool for multiparameter visualization and analysis of nanoparticle molecular dynamics in live cells.

Differential N- and O-glycosylation signatures of HIV-1 Gag virus-like particles and coproduced extracellular vesicles.

Human immunodeficiency virus 1 (HIV‐1) virus‐like particles (VLPs) are nanostructures derived from the self‐assembly and cell budding of Gag polyprotein. Mimicking the native structure of the virus and being noninfectious, they represent promising candidates for the development of new vaccines as they elicit a strong immune response. In addition to this, the bounding membrane can be functionalized with exogenous antigens to target different diseases. Protein glycosylation depends strictly on the production platform and expression system used and the displayed glycosylation patterns may influence downstream processing as well as the immune response. One of the main challenges for the development of Gag VLP production bioprocess is the separation of VLPs and coproduced extracellular vesicles (EVs). In this study, porous graphitized carbon separation method coupled with mass spectrometry was used to characterize the N‐ and O‐ glycosylation profiles of Gag VLPs produced in HEK293 cells. We identified differential glycan signatures between VLPs and EVs that could pave the way for further separation and purification strategies to optimize downstream processing and move forward in VLP‐based vaccine production technology.

Effect of hydrophobicity on distinct anticancer mechanism of antimicrobial peptide chensinin-1b and its lipoanalog PA-C1b in breast cancer cells.

Chensinin-1b and its lipoanalogs demonstrate different anticancer activities against selected cancer cells, and the anticancer activity of PA-C1b is improved up to 3-fold compared with that of the parent peptide chensinin-1b. However, detailing the mechanism of action of these peptides is required to better understand the structure-function relationship. In this study, chensinin-1b and PA-C1b were selected as the representative peptides to investigate the mode of action in cancer cells. The results indicated that the boundary of the cell membrane was broken when the cells were treated with chensinin-1b, while that of cells treated with PA-C1b remained intact based on morphological changes. Apoptosis assays indicated that PA-C1b induced MCF-7 cancer cell apoptosis, while chensinin-1b mainly damaged the cell membrane. MCF-7 cancer cells treated with the peptides induced the loss of mitochondrial membrane potential, and cytochrome c was released from mitochondria, but PA-C1b enhanced ROS generation. Additionally, PA-C1b uptake occurred via an energy-dependent pathway and was inhibited by selected endocytosis inhibitors. Furthermore, treatment of MCF-7 cells with PA-C1b suppressed Bcl-2 mRNA levels and increased Bax mRNA levels, upregulated the expression of the proapoptotic protein Bax and downregulated the expression of the antiapoptotic protein Bcl-2. These results indicate that the anticancer mechanism of AMPs may be considerably affected by only a slight difference in the hydrophobicity of the two peptides; and such a study may facilitate the design of novel peptide-based anticancer agents.

Comparative molecular dynamics simulation studies of realistic eukaryotic, prokaryotic, and archaeal membranes

The OPM (Orientation of Proteins in Membranes) database currently holds, classifies, and annotates around 14,000 three-dimensional structures of transmembrane and peripheral membrane proteins and peptides positioned with respect to membrane boundaries. Developing uniform templates of biological membranes with realistic native-like lipid composition would provide a convenient and accurate platform for researchers who simulate membrane-associated proteins and peptides in natural environments. In this study, for the first time, we performed the standardized molecular dynamic simulations and comparative analysis of structures and properties of 18 native-like membrane models.

Condensed, Microtubule-coating Thin Organelles for Orthogonal Translation in Mammalian Cells

Membraneless organelles are capable of selectively performing complex tasks in living cells despite dynamically exchanging with their surroundings. This is an exquisite example how self-organization of proteins and RNAs can lead to more complex functionalities in living systems. Importantly, the absence of a membrane boundary can enable easier access to larger macromolecular complexes that can be challenging to be transported across a membrane. We previously formed orthogonally translating designer membraneless organelles by combining phase separation with kinesin motor proteins to highly enrich engineered translational factors in large organelles. We also showed that even submicron thick designer organelles can be formed, by mounting them onto membranes, which, presumable assisted by 2D condensation, leads to thin film-like condensates. In this study we show that orthogonal translation can also be built with fiber-like appearing organelles. Here, the microtubule-end binding protein EB1 was used to form fiber-like OT organelles along the microtubule cytoskeleton that perform highly selective and efficient orthogonal translation. We also show an improved simplified design of OT organelles. Together this extends OT organelle technology and demonstrates that the microtubule cytoskeleton is a powerful platform for advanced synthetic organelle engineering.

Hetero‐Lattice Intergrown and Robust MOF Membranes for Polyol Upgrading

AbstractMetal–organic framework membranes are frequently used in gas separations, but rare in pervaporation for liquid chemical upgrading, especially for separating water from polyols, due to lack of highly compact and robust micro‐architecture. Here, we report hetero‐lattice intergrown membranes in which amino‐MIL‐101 (Cr) particles embedded into the micro‐gaps of MIL‐53 (Al) rod arrays after secondary growth. By means of high‐resolution TEM and two‐dimensional topologic simulation, the connection between these two distinct MOF lattices at the molecular‐level and their crystallographic geometry harmony is identified, which leads to a close‐knit structure at the crystal boundaries of membranes. Typically, the membrane shows a separation factor as high as 13 000 for a 90/10 ethanediol/water solution in pervaporation, yields polymer‐grade ethanediol, and saves ca. 32 % of energy consumption vs. vacuum distillation. It has a highly robust micro‐architecture, with great tolerance to high pressure, durability against ultrasonic therapy and long‐term separation stability over 600 h.

Hetero-Lattice Intergrown and Robust MOF Membranes for Polyol Upgrading.

Metal-organic framework membranes are frequently used in gas separations, but rare in pervaporation for liquid chemical upgrading, especially for separating water from polyols, due to lack of highly compact and robust micro-architecture. Here, we report hetero-lattice intergrown membranes in which amino-MIL-101 (Cr) particles embedded into the micro-gaps of MIL-53 (Al) rod arrays after secondary growth. By means of high-resolution TEM and two-dimensional topologic simulation, the connection between these two distinct MOF lattices at the molecular-level and their crystallographic geometry harmony is identified, which leads to a close-knit structure at the crystal boundaries of membranes. Typically, the membrane shows a separation factor as high as 13 000 for a 90/10 ethanediol/water solution in pervaporation, yields polymer-grade ethanediol, and saves ca. 32 % of energy consumption vs. vacuum distillation. It has a highly robust micro-architecture, with great tolerance to high pressure, durability against ultrasonic therapy and long-term separation stability over 600 h.

Применение активированной кондиционированной плазмы у пациентов с макулярным разрывом

Objective. To evaluate and summarize the results, as well as to conduct a comparative analysis of the treatment of patients with macular rupture with autoplasm, using a Rotofix 32A Centrifuge and Arthrex ACP systems to obtain autologous conditioned plasma (АСР) with previously used surgical methods. Material and methods. The study conducted a comparative analysis of the results of treatment of patients with macular rupture, with a corrected visual acuity of more than 0.08 (according to the Golovin–Sivtsev table). Group 1 (prospective analysis) included the results of treatment using peeling of the inner boundary membrane with a gas/air tamponade in combination with the application of AСР (4 eyes, 4 patients). In the 2nd group (retrospective analysis of the medical history), surgical treatment was limited to the peeling of the inner boundary membrane with a gas/air tamponade (8 eyes, 8 patients). The parameters were analyzed after 3.0±0.5 and 6.0±0.5 months with assessment of maximum corrected visual acuity (MCOZ), optical coherence tomography (OCT), color photography. Closure of the macular gap was assessed at 6 months of follow-up when comparing the groups. Results. No complications were detected in both groups during the observation period. According to visometry and OCT data, the best functional results were obtained in group 1. The average visual acuity after 6 months was 0.4±0.1. Conclusion. The study found that the use of the peeling of the inner boundary membrane with gas/air tamponade and the use of platelet-derived mass increased the probability of rupture closure.

Signal transduction from ligand-receptor binding associated with the formation of invadopodia in an invasive cancer cell

<abstract> <p>Invadopodia are finger-like protrusions that are commonly spotted at the membrane of the invasive cancer cell. These structures are a major cause of death among cancer patients through metastasis process. Signal transduction stimulated upon contact between ligand and membrane receptors is identified as one of key factors in invadopodia formation. In this study, a time-dependent mathematical model of signal and ligand is investigated numerically. The moving boundary of plasma membrane is taken as a zero-level set function and is moved by the velocity that accounted as the difference of gradient between intra-cellular signal and extra-cellular ligand. The model is solved using a combination of ghost with linear extrapolation and finite difference methods. The results showed that the stimulation of signal from membrane associated ligand consequently moved the plasma membrane outward as time increases. The highest densities of signal and ligand are recorded on the membrane and slowly diffused into intra-cellular and extra-cellular regions, respectively.</p> </abstract>

Large Scale Direct Shear Box Tests on Gravels

The determination of shear strength characteristics of gravelly soils is difficult through the use of conventional small scale, triaxial or simple shear testing devices in the laboratory due to membrane compliance and boundary effects; or due to inconsistent penetration resistances measured as part of standard or cone penetration testing in the field. These limitations require the use of available empirical or semi-empirical relationships or the execution of large scale laboratory or field tests. In the literature there exists inconsistent, and large range of recommendations for shear strength parameters. Within the confines of this study, direct shear box test results performed on poorly- (GP) and well-graded (GW) gravel samples with initial void ratio ranging from 0.42 to 0.53 are presented, which are tested under effective normal stresses ranging from 77 to 205 kPa. The estimated peak secant-angles of shearing resistances vary in the range of 49 to 54 degrees. On the basis of volumetric change vs. shear strain responses, the peak angle of dilation and elastic Poisson’s ratio are estimated to vary in the range of 10-16 degrees and 0.28-0.39, respectively. These estimated values are compared with available literature.

Technique for investigation of the shape changes of wafers and thin-film membranes by using geomorphometric approaches

We discuss a technique for investigating changes in complex topography and shape of structures using geomorphometric methods to study surfaces of wafers and membranes formed by the Bosch process. The wafers were analyzed before and after the deposition of the SiO2 layer. The membranes were analyzed during the bulge testing. The study was carried out using maps of the catchment area and principal curvatures taking into account artifacts of the approximation of experimental data. We found a correspondence between the distribution of lines connecting the highest surface areas before and after the deposition of the SiO2 layer on the wafers. For membranes with structure: Al(0.8 μm)/SiO2(0.6 μm)/Al(1.1 μm), pSi*(0.8 μm)/SiNx(0.13 μm)/SiO2, Al(0.6 μm) we also found that features of membrane boundaries are mainly caused by their initial shape rather than change under the action of an applied pressure. The advantages of geomorphometric methods for studying changes in the shape of wafers and thin-film membranes in technological processes for the manufacturing of microelectronic devices are shown in comparison with traditional methods for analyzing surface topography maps. Keywords: thin films, membrane, defect, mechanical characteristics, mechanical stresses, deformation, deflection, strain, microelectromechanical systems, MEMS, circular membrane, silicon substrate, optical profilometry, overpressure, geomorphometry, Gaussian curvature, warpage, principal curvatures, wafer, bulge testing, bulging method, thin-layer coating, digital elevation models, DEM, surface, topography.

Thin membrane-based potentiometric sensors for sensitive detection of polyions.

A novel protocol for development of sensitive and rapid polymeric membrane polyion sensitive electrodes has been explored in this work. In contrast to the traditional polyion electrodes which usually have a sensing membrane thickness of 100∼200 μm, a thin membrane electrode with a membrane thickness of 5 μm is proposed to detect polyions. By using such thin membrane configuration, the diffusion of polyions from the organic boundary layer into the bulk of the membrane can be effectively blocked. The induced accumulation of polyions in the membrane boundary layer largely enhances the obtained potential response. It has been found that the proposed electrode shows a remarkably improved sensitivity and measurement time over conventional potentiometric polyion sensors based on the thick membranes. By using protamine as a model of polyions, the new concept offers a detection limit nearly two orders of magnitude lower than those obtained by the traditional thick-membrane polyion electrodes for potentiometric measurements of polyions. The proposed polyion sensing platform offers great promise in the sensitive and rapid detection of polyions as well as other polyion-involved bioanalyses.

Методика исследования изменения формы пластин и тонкопленочных мембран с использованием геоморфометрических подходов

We discuss a technique for investigating changes in complex topography and shape of structures using geomorphometric methods to study surfaces of wafers and membranes formed by the Bosch process. The wafers were analyzed before and after the deposition of the SiO2 layer. The membranes were analyzed during the bulge testing. The study was carried out using maps of the catchment area and principal curvatures taking into account artifacts of the approximation of experimental data. We found a correspondence between the distribution of lines connecting the highest surface areas before and after the deposition of the SiO2 layer on the wafers. For membranes with structure: Al (0.8 μm)/SiO2 (0.6 μm)/Al (1.1 μm), pSi*(0.8 μm)/SiNx (0.13 μm)/SiO2, Al (0.6 μm) – we also found that features of membrane boundaries are mainly caused by their initial shape rather than change under the action of an applied pressure. The advantages of geomorphometry methods for studying changes in the shape of wafers and thin-film membranes in technological processes for the manufacturing of microelectronic devices are shown in comparison with traditional methods for analyzing surface topography maps.

Функциональная и клиническая морфология пространств Вирхова-Робина: от первоисточника до новейших теорий

Morphology of cerebrospinal fluid flow structures in CNS is an important and complex area of research and is associated with the problems of metabolites transport, including pathological ones in neurodegenerative pathology, e.g., Alzheimer's disease. Since Virchow and Robin first described the perivascular spaces in the 19th century, their role in the transport of cerebrospinal fluid and intracerebral metabolites has been established. On the grounds of the 20th century studies, a modern theory of intracerebral liquor transport of metabolites, the glymphatic system theory, has emerged, creating the basis for new areas of treatment of neurodegenerative diseases. The article presents an overview of the history of description and study of CNS perivascular transport pathways, terminology issues and clinical problems such as amyloid transport and its disruption as a mechanism of Alzheimer's disease and glaucoma. We present our own descriptive data on the morphology of the perivascular spaces (PVS) of the rat brain in normal and simulated glaucoma-like increases in intraocular pressure. Structures corresponding to perivascular spaces (PVS) in their original description are present in the rat brain along arteries and arterioles. They are represented by intervals between the medium and adventitia, in the adventitia, and between the adventitia and the inner pial fibrous layers. At the level of capillaries they are closed. In the venous link there are only paravenular spaces between the vascular wall and glial boundary membrane. Periarterial-like leptomeningeal structures and spaces are absent. In glaucoma-like experimental increase in intraocular pressure, the periarterial spaces respond with expansion, and in addition to them, intermyocyte spaces are formed in the medium On the basis of glymphatic theory we propose the possibility of regulation of intracerebral metabolic transport and hydrodynamic system”eye - optic nerve -brain” via vascular mechanisms of perivascular transport.

Air bubbling assisted solar-driven submerged vacuum membrane distillation for aquaculture seawater desalination

Submerged vacuum membrane distillation (S-VMD) was proposed in this work to desalinate aquaculture seawater. In this S-VMD without feed-pumping system, the hydrophobic hollow fibre membranes are fully immersed in the feed tank with internal coil heated by solar evacuated tube collector. In this study, indoor test under steady-state condition was compared to the outdoor test under solar intensity variation. The system’s feasibility and practicality were investigated. In the daily outdoor performance test, the solar-powered S-VMD system obtained permeate flux at 2.1–5.2 kg/m2h, depending on the solar intensity profile. Air bubbling as enhanced flow promoter and anti-fouling technique was employed to overcome the polarizations at the membrane boundary layer. Compared to non-bubbling, the bubbling approach in the S-VMD system effectively achieved higher flux and fouling reduction with better permeate quality. It is suggested that the system can be applied in energy-deprived and space-constricted remote area, particularly marine aquaculture farm to produce clean water for coastal fishery communities.

Cryo-EM of the ATP11C flippase reconstituted in Nanodiscs shows a distended phospholipid bilayer inner membrane around transmembrane helix 2

ATP11C is a member of the P4-ATPase flippase family that mediates translocation of phosphatidylserine (PtdSer) across the lipid bilayer. In order to characterize the structure and function of ATP11C in a model natural lipid environment, we revisited and optimized a quick procedure for reconstituting ATP11C into Nanodiscs using methyl-β-cyclodextrin as a reagent for the detergent removal. ATP11C was efficiently reconstituted with the endogenous lipid, or the mixture of endogenous lipid and synthetic dioleoylphosphatidylcholine (DOPC)/dioleoylphosphatidylserine (DOPS), all of which retained the ATPase activity. We obtained 3.4 Å and 3.9 Å structures using single-particle cryo-electron microscopy (cryo-EM) of AlF- and BeF-stabilized ATP11C transport intermediates, respectively, in a bilayer containing DOPS. We show that the latter exhibited a distended inner membrane around ATP11C transmembrane helix 2, possibly reflecting the perturbation needed for phospholipid release to the lipid bilayer. Our structures of ATP11C in the lipid membrane indicate that the membrane boundary varies upon conformational changes of the enzyme and is no longer flat around the protein, a change that likely contributes to phospholipid translocation across the membrane leaflets.

A critical analysis on ion transport of organic acid mixture through an anion-exchange membrane during electrodialysis

The effect of the composition and pH of solutions on the transport of organic acids species in the anion exchange membrane (AEM) and adjacent diffusion layers has been investigated using voltamperomertry and chronopotentiometry. Carboxylic acids of varying number of carboxylic groups (acetic, malic and citric acid) were selected and their individual concentration in the mixture was varied to understand the influence of one molecule on the transport of other molecule in their mixture. Shape of the I–V and chronopotentiometric curves was influenced by pH and concentration. Detection of two limiting current densities (LCD) in I–V curves and inflection points in chronopotentiometric curves are due to change in species that are being transported in boundary layers and membrane. Results showed that LCD, resistance to ionic transport and concentration polarization were related to molar concentration and anionic equivalent charge calculated from Hydra-Medusa. Smaller size, higher mobility and charge density delayed the formation of concentration polarization. Electrolytes having ionic species with more anionic equivalent charge and larger Stokes radii were responsible for an early activation of overlimiting mechanisms and shorter plateau in I–V curve.

Practical computation of the diffusion MRI signal based on Laplace eigenfunctions: permeable interfaces.

The complex transverse water proton magnetization subject to diffusion-encoding magnetic field gradient pulses in a heterogeneous medium such as brain tissue can be modeled by the Bloch-Torrey partial differential equation. The spatial integral of the solution of this equation in realistic geometry provides a gold-standard reference model for the diffusion MRI signal arising from different tissue micro-structures of interest. A closed form representation of this reference diffusion MRI signal, called matrix formalism, which makes explicit the link between the Laplace eigenvalues and eigenfunctions of the tissue geometry and its diffusion MRI signal, was derived 20 years ago. In addition, once the Laplace eigendecomposition has been computed and saved, the diffusion MRI signal can be calculated for arbitrary diffusion-encoding sequences and b-values at negligible additional cost. In a previous publication, we presented a simulation framework that we implemented inside the MATLAB-based diffusion MRI simulator SpinDoctor that efficiently computes the matrix formalism representation for biological cells subject to impermeable membrane boundary conditions. In this work, we extend our simulation framework to include geometries that contain permeable cell membranes. We describe the new computational techniques that allowed this generalization and we analyze the effects of the magnitude of the permeability coefficient on the eigendecomposition of the diffusion and Bloch-Torrey operators. This work is another step in bringing advanced mathematical tools and numerical method development to the simulation and modeling of diffusion MRI.

A three-dimensional DEM modelling of triaxial test on gas hydrate-bearing sediments considering flexible boundary condition

The discrete element method (DEM) has been widely used to investigate the mechanical properties of gas hydrate-bearing sediments (GHBS). However, a flexible membrane boundary has not been incorporated into three-dimensional DEM modelling. Moreover, the roles of hydrates in stress transmission have not been comprehensively interpreted from a particulate scale point of view. This study adopted the finite difference method (FDM)-discrete element method (DEM) coupling method to establish the flexible boundary condition to capture the failure modes of GHBS and categorized the overall contact set into three contact subsets (i.e., soil-soil, soil-hydrate and hydrate-hydrate contact subsets) in a way that the stress transmission characteristics of hydrates can be identified. The simulated macroscale mechanical responses demonstrate a favourable agreement against the experimental results. The results show that the sample with a low hydrate saturation shows a single slant shear failure zone, while the sample with a high hydrate saturation shows an X-shape shear failure zone. The particulate scale analysis shows that the soil-hydrate contact subset not only plays a critical role in stabilizing the strong force chains but also has a significant contribution to the deviatoric stress. By contrast, the hydrate-hydrate contact subset accounts for a small contribution to the deviatoric stress.