Membrane Tube Research Articles

WDR91 specifies the endosomal retrieval subdomain for retromer-dependent recycling.

Retromer-dependent endosomal recycling of membrane receptors requires Rab7, sorting nexin (SNX)-retromer, and factors that regulate endosomal actin organization. It is not fully understood how these factors cooperate to form endosomal subdomains for cargo retrieval and recycling. Here, we report that WDR91, a Rab7 effector, is the key factor that specifies the endosomal retrieval subdomain. Loss of WDR91 causes defective recycling of both intracellular and cell surface receptors. WDR91 interacts with SNXs through their PX domain, and with VPS35, thus promoting their interaction with Rab7. WDR91 also interacts with the WASH subunit FAM21. In WDR91-deficient cells, Rab7, SNX-retromer, and FAM21 fail to localize to endosomal subdomains, and endosomal actin organization is impaired. Re-expression of WDR91 enables Rab7, SNX-retromer, and FAM21 to concentrate at WDR91-specific endosomal subdomains, where retromer-mediated membrane tubulation and release occur. Thus, WDR91 coordinates Rab7 with SNX-retromer and WASH to establish the endosomal retrieval subdomains required for retromer-mediated endosomal recycling.

Autoimmunity to extracellular matrix in inflammatory bowel disease: antibody to intestinal epithelial basement membrane and renal tubules in severe ulcerative colitis and Crohn disease

Autoimmunity to extracellular matrix in inflammatory bowel disease: antibody to intestinal epithelial basement membrane and renal tubules in severe ulcerative colitis and Crohn disease

Opto-katanin, an optogenetic tool for localized, microtubule disassembly

Microtubules are cytoskeletal polymers that separate chromosomes during mitosis and serve as rails for intracellular transport and organelle positioning. Manipulation of microtubules is widely used in cell and developmental biology, but tools for precise subcellular spatiotemporal control of microtubules are currently lacking. Here, we describe a light-activated system for localized recruitment of the microtubule-severing enzyme katanin. This system, named opto-katanin, uses targeted illumination with blue light to induce rapid, localized, and reversible microtubule depolymerization. This tool allows precise clearing of a subcellular region of microtubules while preserving the rest of the microtubule network, demonstrating that regulation of katanin recruitment to microtubules is sufficient to control its severing activity. The tool is not toxic in the absence of blue light and can be used to disassemble both dynamic and stable microtubules in primary neurons as well as in dividing cells. We show that opto-katanin can be used to locally block vesicle transport and to clarify the dependence of organelle morphology and dynamics on microtubules. Specifically, our data indicate that microtubules are not required for the maintenance of the Golgi stacks or the tubules of the endoplasmic reticulum but are needed for the formation of new membrane tubules. Finally, we demonstrate that this tool can be applied to study the contribution of microtubules to cell mechanics by showing that microtubule bundles can exert forces constricting the nucleus.

Single-stage tubular and multistage planar systems of passive permeate-side-heated solar membrane distillation

Scarcity of drinking water is a global problem and especially serious in rural areas of developing countries. Passive permeate-side-heated interfacial-heating solar membrane distillation has been shown recently as a promising system for off-grid distributed water and wastewater treatment. In this study, single-stage tubular systems were developed by giving the poly(vinylidene fluoride) (PVDF) membrane (pore size: 0.45 µm) a tubular structure with the outer surface (i.e., the permeate side) coated with carbon black NPs which absorbed solar thermal energy and evaporated the feedwater inside the membrane tube. Under natural sunlight, the vertical tubular system had a production rate of distilled water per footprint of 0.67‒2.06 kg m−2 day−1 throughout the year, 71% higher than the single-stage planar system on average. The three-stage planar systems were developed by overlapping three single-stage modules. Two adjacent modules shared a common copper sheet that serves as both the top of the condensation chamber of the preceding stage and the bottom of the feedwater chamber of the following stage. The copper sheet can partially transfer the condensation heat of the preceding stage to the feedwater of the following stage, thus enhancing the system energy efficiency (ƞsys) in producing distilled water. The ƞsys and distillate flux of the three-stage systems were 62% and 5.01 kg m−2 day−1, respectively, at the average daytime irradiance of 422 W m−2, 34% higher than the single-stage planar systems.

Programmable soft valves for digital and analog control

In soft devices, complex actuation sequences and precise force control typically require hard electronic valves and microcontrollers. Existing designs for entirely soft pneumatic control systems are capable of either digital or analog operation, but not both, and are limited by speed of actuation, range of pressure, time required for fabrication, or loss of power through pull-down resistors. Using the nonlinear mechanics intrinsic to structures composed of soft materials-in this case, by leveraging membrane inversion and tube kinking-two modular soft components are developed: a piston actuator and a bistable pneumatic switch. These two components combine to create valves capable of analog pressure regulation, simplified digital logic, controlled oscillation, nonvolatile memory storage, linear actuation, and interfacing with human users in both digital and analog formats. Three demonstrations showcase the capabilities of systems constructed from these valves: 1) a wearable glove capable of analog control of a soft artificial robotic hand based on input from a human user's fingers, 2) a human-controlled cushion matrix designed for use in medical care, and 3) an untethered robot which travels a distance dynamically programmed at the time of operation to retrieve an object. This work illustrates pathways for complementary digital and analog control of soft robots using a unified valve design.

Cancer Neuroscience

The nervous system integrates and processes information to act as master regulator of various vital, biological processes. However, increasing data suggest that the nervous system is also a key player in the initiation of cancer and cancer progression. Following the tenet that oncology follows ontogeny, it has been shown that brain tumors follow neural developmental processes. Incurable gliomas form neurite-like membrane tubes called tumor microtubes and are controlled by neurodevelopmental pathways. Tumor microtubes are used for invasion, proliferation and interconnection with other tumor cells, forming a tumor network that is therapeutically resistant. Additionally, neurons can activate tumor cells via glutamatergic synapses to drive tumor invasion and growth. The most recent knowledge of brain cancer neuroscience presented here with a focus on brain tumours has already led to new approaches for antitumour treatment.

Phosphatidylinositol-4-kinase 2α enhances phagosomal TLR signaling and MHC class II presentation in mouse dendritic cells

Toll like receptor (TLR) recruitment to bacteria-containing phagosomes and subsequent TLR signaling in dendritic cells (DCs) are essential to initiate anti-microbial immune responses, but the mechanisms underlying TLR trafficking to phagosomes are poorly characterized. We previously showed that the endosomal adaptor protein-3 (AP-3) optimizes TLR4 and MyD88 recruitment to phagosomes and favors phagosomal TLR signaling to proinflammatory cytokine secretion, membrane tubulation and MHC-II presentation. However, AP-3 functions indirectly in these activities. We hypothesized that this reflects AP-3’s role in endolysosomal protein sorting, and that defining direct targets of AP-3 sorting will elucidate new membrane pathways controlling TLR signaling and anti-bacterial immune responses. We have identified that one such AP-3 effector is phosphatidylinositol (PI)-4-kinase 2α (PI4K2α), which generates PI4P, a lipid reported to engage the TLR adaptor TIRAP to recruit MyD88 and TIRAP to membranes. We show that PI4K2α is recruited to nascent LPS-bead phagosomes in wild-type (WT) bone marrow-derived (BM) DCs and that its recruitment is reduced in AP-3-deficient pearl BMDCs, both by immunofluorescence microscopy and immunoblotting of isolated phagosomes. Moreover, both PI4K2α-GFP and PI4P co-localize with LPS/OVA-texas red bead phagosomes 2 hours after uptake in WT DCs and on phagotubules. The formation of tubules from phagosomes in BMDCs is impaired upon knock-down of PI4K2α but not PI4K2β. This correlates with reduced MHC-II presentation of particulate Ealpha antigen and impaired T cell activation. Additionally, after LPS priming, IL-1β secretion induced by multiple stimuli is reduced in BMDCs by PI4K2α knock-down compared to controls, suggesting that PI4K2α is necessary for optimal inflammasome activity, likely by impacting either priming (via TLR signaling) or NLR stimulation (by increasing membrane surface via tubulation). In summary, PI4K2α is a novel regulator of phagosomal signaling required for TLR recruitment to phagosomes and downstream signaling pathways in DCs.

Recruitment of Irgb6 to the membrane is a direct trigger for membrane deformation.

Irgb6 is a member of interferon γ-induced immunity related GTPase (IRG), and one of twenty “effector” IRGs, which coordinately attack parasitophorous vacuole membrane (PVM), causing death of intracellular pathogen. Although Irgb6 plays a pivotal role as a pioneer in the process of PVM disruption, the direct effect of Irgb6 on membrane remained to be elucidated. Here, we utilized artificial lipid membranes to reconstitute Irgb6-membrane interaction in vitro, and revealed that Irgb6 directly deformed the membranes. Liposomes incubated with recombinant Irgb6 were drastically deformed generating massive tubular protrusions in the absence of guanine nucleotide, or with GMP-PNP. Liposome deformation was abolished by incubating with Irgb6-K275A/R371A, point mutations at membrane targeting residues. The membrane tubules generated by Irgb6 were mostly disappeared by the addition of GTP or GDP, which are caused by detachment of Irgb6 from membrane. Binding of Irgb6 to the membrane, which was reconstituted in vitro using lipid monolayer, was stimulated at GTP-bound state. Irgb6 GTPase activity was stimulated by the presence of liposomes more than eightfold. Irgb6 GTPase activity in the absence of membrane was also slightly stimulated, by lowering ionic strength, or by increasing protein concentration, indicating synergistic stimulation of the GTPase activity. These results suggest that membrane targeting of Irgb6 and resulting membrane deformation does not require GTP, but converting into GTP-bound state is crucial for detaching Irgb6 from the membrane, which might coincident with local membrane disruption.

Performance analysis of a cross-flow transport membrane condenser for heat and moisture recovery from flue gas

Cross-flow transport membrane condenser consisted of numerous ceramic membrane tubes is a novel device for heat and moisture recovery from flue gas. Fluid flow, heat and mass transfer in the membrane condenser are investigated by numerically solving the conservation equations for flue gas stream, membrane and water stream in a coupled way. Compared with the previous researches which neglected the variations of velocity, temperature and vapor fraction in the water flow direction, in this study the three-dimensional RNG k-ε turbulence model and laminar model are used in flue gas stream and water stream, respectively. The velocity, temperature and humidity contours of the membrane condenser, as well as the heat and water fluxes of the membrane surface are plotted. It is found that the variations of temperature, heat and mass fluxes on the membrane surface are significant. The latent heat flux accounts for more than 90% of the total heat flux. Besides, with the rise of flue gas velocity and packing fraction, the heat and water fluxes increase slightly, but the flow resistance of flue gas stream grows quickly. According to the analysis of thermal resistances, it is noticed that the thermal resistance at the water side is beyond 70% of the total resistance. The numerical results can provide the foundation for the engineering design and optimization of the transport membrane condenser.

Thrombus formation during ECMO: Insights from a detailed histological analysis of thrombus composition

ObjectivesIntra‐device thrombosis remains one of the most common complications during extracorporeal membrane oxygenation (ECMO). Despite anticoagulation, approximately 35% of patients develop thrombi in the membrane oxygenator, pump heads, or tubing. The aim of this study was to describe the molecular and cellular features of ECMO thrombi and to study the main drivers of thrombus formation at different sites in the ECMO circuits. Approach and ResultsThrombi (n = 85) were collected immediately after veno‐arterial‐(VA)‐ECMO circuit removal from 25 patients: 23 thrombi from the pump, 25 from the oxygenator, and 37 from the tubing. Quantitative histological analysis was performed for the amount of red blood cells (RBCs), platelets, fibrin, von Willebrand factor (VWF), leukocytes, and citrullinated histone H3 (H3Cit). ECMO thrombi consist of a heterogenous composition with fibrin and VWF being the major thrombus components. A clustering analysis of the four major histological parameters identified two typical thrombus types: RBC‐rich and RBC‐poor/fibrin‐rich thrombi with no significant differences in VWF and platelet content. Thrombus composition was not associated with the thrombus location, except for higher amounts of H3Cit that were found in pump and oxygenator thrombi compared to tubing samples. We observed higher blood leukocyte count and lactate dehydrogenase levels in patients with fibrin‐rich thrombi. ConclusionWe found that thrombus composition is heterogenous, independent of their location, consisting of two types: RBC‐rich and a fibrin‐rich types. We also found that NETs play a minor role. These findings are important to improve current anticoagulation strategies in ECMO.

Preprint Highlight: Sugar transporter Slc37a2 regulates bone metabolism via a dynamic tubular lysosomal network in osteoclasts.

Despite the importance of osteoclast secretory lysosomes (SLs) in bone digestion and resorption, the proteins that reside on SLs are undercharacterized. The authors show that SLC37a2, a unique member of the SLC37 family of sugar ER transporters, localizes to osteoclast SLs and SL tubular networks that support bone resorption. SLC37a2-deficient osteoclasts showed impaired SL membrane tubulation and increased SL size and accumulated monosaccharides, reminiscent of lysosomal storage disorders. Mice lacking SLC37a2 had increased bone mass and strength. As SLC transporters quickly become recognized as metabolic hot spots, SLC37a2 is emerging as a new regulator of lysosomal membrane dynamics and a promising therapeutic target for metabolic bone diseases.

Research on mass transfer characteristics of the flue gas dehydration using ceramic membrane transport condensers

• Building an experimental platform for flue gas dehydration with the ceramic membrane tube. • Circulating water and purge gas are used as the cooling medium. • The operating parameters are divided into flue gas and cooling medium parameters. • Correlation analysis of permeate flux and intrinsic factors influenced by operating parameters. • Excessive transmembrane pressure difference can damage the selective permeability of ceramic membranes. The direct discharge of flue gas from the coal fired boiler can result in significant water loss. Membrane separation technology is an effective means to solve the flue gas dehydration problem. Based on the permeation characteristics of porous membrane materials, ceramic membrane method flue gas dehydration is a complex mass transfer process. In this paper, the ceramic membrane transport condensers were built with circulating water, positive pressure purge gas and negative pressure purge gas as the cooling medium, respectively. Changing flue gas parameters and cooling medium parameters, the correlation coefficients of water vapor pressure difference, transmembrane pressure difference and Reynolds number with permeate flux were investigated. The results showed that the key factors that determine the permeate flux were slightly different with the different experimental conditions. Changing the flue gas temperature or the cooling medium temperature has an obvious effect on the water vapor pressure difference. There is a significant correlation between the water vapor pressure difference and the permeate flux. Changing the flue gas flow or the cooling medium flow, the water vapor pressure difference is less variable, and the transmembrane pressure difference is not the key factor affecting the permeate flux, and the Reynolds number is the key factor affecting the permeate flux. Meanwhile, the experimental process revealed that an excessive transmembrane pressure difference can cause non-condensable gases in the flue gas to enter the cooling water tank.

Stability of the aneurysm-type solution in a membrane tube with localized wall thinning filled with a fluid with a non-constant velocity profile

We perform the stability analysis of bulging localized structures on the wall of a fluid-filled axisymmetric membrane elastic tube. The wall of the tube is assumed to be subjected to localized thinning. The problem has no translational invariance anymore, hence the stability of a bulging wave centered in the point of the localization of imperfection is usual, and not orbital stability up to a shift as in the case of translationally invariant governing equations. Motionless wave solutions of the governing equations having the form of a localized bulging are called throughout the paper aneurysm solutions. We assume that the fluid is subjected to the power law for viscous friction of a non-Newtonian fluid, and also that the viscosity of the fluid does not play a significant role and it can be neglected. The velocity profile remains not constant along the cross section of the tube (even in the absence of the viscosity) because no-slip boundary conditions are performed on the tube walls. Stability is established by demonstrating the non-existence of the unstable eigenvalues with a positive real part of the linearized problem. This is achieved by constructing the Evans function depending only on the spectral parameter, analytic in the right half of the complex plane Ω+ and which zeroes in Ω+ coincide with the unstable eigenvalues of the problem. The non-existence of zeroes of the Evans function is performed using the argument principle from the analysis of complex variable. Finally, we discuss the possibility of applying of the results of the present analysis to the aneurysm formation in damaged human vessels under the action of the internal pressure.

Membrane Remodeling Due to a Mixture of Multiple Types of Curvature Proteins.

We present an extension of the Monte Carlo based mesoscopic membrane model, where the membrane is represented as a dynamically triangulated surface and the proteins are modeled as anisotropic inclusions formulated as in-plane nematic field variables adhering to the deformable elastic sheet. In the extended model, we have augmented the Hamiltonian to study membrane deformation due to a mixture of multiple types of curvature generating proteins. This feature opens the door for understanding how multiple kinds of curvature-generating proteins may be working in a coordinated manner to induce desired membrane morphologies. For example, among other things, we study membrane deformations and tubulation due to a mixture of positive and negative curvature proteins as mimics of various proteins from BAR domain family. We also study the effect of membrane anisotropy that manifests as differential binding affinity and organization of curvature proteins, leading to insights into the tightly regulated cargo sorting and transport processes. Our simulation results show different morphology of deformed vesicles that depend on membrane tension, the curvatures and number of the participating proteins as well as on protein-protein and membrane-protein interactions.

Simulation and techno-economic analysis of moisture and heat recovery from original flue gas in coal-fired power plants by macroporous ceramic membrane

Macroporous ceramic membrane can be used to recover heat and water vapor from the original flue gas in coal-fired power plants, which is conducive to saving water and improving the economic benefits of power generation. However, the overall mass and heat transfer model for the application of membrane modules has not been established at present, and the impact of various parameters on economic benefits has rarely been studied. Therefore, a heat and mass transfer model for 45,600 membrane tubes in a 330 MW coal-fired power plant was established in this paper. Then EBSILON software was applied to simulate the entire thermal system to analyze the economic benefits under different parameters, including cooling water temperatures, cooling water flowrates, turbine heat acceptance operating conditions, and ceramic membrane areas. Finally, its net present value was calculated. The results indicated that the cost recovery time of the transport membrane condenser was 6.85 years when the cooling water temperature is 25 °C and cooling water flowrate is 1000 t/h, and the coal consumption rate was reduced by 0.521 g/(kW·h), which provided theoretical and empirical support for industrial applications.

Encapsulated bacteria deform lipid vesicles into flagellated swimmers

We study a synthetic system of motile Escherichia coli bacteria encapsulated inside giant lipid vesicles. Forces exerted by the bacteria on the inner side of the membrane are sufficient to extrude membrane tubes filled with one or several bacteria. We show that a physical coupling between the membrane tube and the flagella of the enclosed cells transforms the tube into an effective helical flagellum propelling the vesicle. We develop a simple theoretical model to estimate the propulsive force from the speed of the vesicles and demonstrate the good efficiency of this coupling mechanism. Together, these results point to design principles for conferring motility to synthetic cells.

Excitable reaction-diffusion waves of curvature-inducing proteins on deformable membrane tubes.

Living cells employ excitable reaction-diffusion waves for internal cellular functions, in which curvature-inducing proteins are often involved. However, the role of their mechanochemical coupling is not well understood. Here, we report the membrane deformation induced by the excitable reaction-diffusion waves of curvature-inducing proteins and the alternation in the waves due to the deformation, using a coarse-grained simulation of tubular membranes with a modified FitzHugh-Nagumo model. Protein-propagating waves deform tubular membranes and large deformations induce budding and erase waves. The wave speed and shape are determined by a combination of membrane deformation and spatial distribution of the curvature-inducing protein. Waves are also undulated in the azimuthal direction depending on the condition. Rotationally symmetric waves locally deform the tubes into a symmetric shape but maintain a straight shape on average. Our simulation method can be applied to other chemical reaction models and used to investigate various biomembrane phenomena.

CFD analysis and scale up of a baffled membrane reactor for hydrogen production by steam methane reforming

Catalytic membrane reactor (CMR) represents an intensified process that combines the reaction and separation steps. For a high level of productivity, multiple membrane tubes are placed in a CMR, which can lead to the problem of concentration and temperature gradients. This study explores the idea of placing baffles inside the CMR, which is called baffled membrane reactor (BMR). Representative CMR and BMR are compared using computational fluid dynamics (CFD) simulations. First, the CFD model of a single-tube CMR is validated with the published experimental data. The results for a 4-tube CMR and BMR (with 14-baffles) reveal that the baffles lead to complex flow patterns, regions with elevated pressure, reduced concentration gradients and reduced temperature drops. The BMR’s performance is less sensitive to an increase in gas hourly space velocity than that of the CMR. Simulations of a larger-scale BMR shows that the performance improvement over the CMR is retained.

Friction-driven membrane scission by the human ESCRT-III proteins CHMP1B and IST1

The endosomal sorting complexes required for transport (ESCRT) system is an ancient and ubiquitous membrane scission machinery that catalyzes the budding and scission of membranes. ESCRT-mediated scission events, exemplified by those involved in the budding of HIV-1, are usually directed away from the cytosol ("reverse topology"), but they can also be directed toward the cytosol ("normal topology"). The ESCRT-III subunits CHMP1B and IST1 can coat and constrict positively curved membrane tubes, suggesting that these subunits could catalyze normal topology membrane severing. CHMP1B and IST1 bind and recruit the microtubule-severing AAA+ ATPase spastin, a close relative of VPS4, suggesting that spastin could have a VPS4-like role in normal-topology membrane scission. Here, we reconstituted the process invitro using membrane nanotubes pulled from giant unilamellar vesicles using an optical trap in order to determine whether CHMP1B and IST1 are capable of membrane severing on their own or in concert with VPS4 or spastin. CHMP1B and IST1 copolymerize on membrane nanotubes, forming stable scaffolds that constrict the tubes, but do not, on their own, lead to scission. However, CHMP1B-IST1 scaffolded tubes were severed when an additional extensional force was applied, consistent with a friction-driven scission mechanism. We found that spastin colocalized with CHMP1B-enriched sites but did not disassemble the CHMP1B-IST1 coat from the membrane. VPS4 resolubilized CHMP1B and IST1 without leading to scission. These observations show that the CHMP1B-IST1 ESCRT-III combination is capable of severing membranes by a friction-driven mechanism that is independent of VPS4 and spastin.

Hydrous Fe-Al-Zr oxide composite filled dialysis membrane tubes for phosphate desorption study from acidic soils

Phosphorus fixation by different soil components is the main problem making it less available to plants. To approximate this biological measure, a method comprising hydrous Fe-Al-Zr ternary mixed oxide (HFAZO) sorbent filled in dialysis membrane tubes (DMT) was developed. The sorbent (HFAZO), which is composed of Fe (60%), Al (25%) and Zr (15%), was synthesized via impregnation method and characterized by XRD, BET, SEM-EDX, FT-IR and FAAS. Its average crystallite size and surface area were found to be 29.59 nm and 107.53 m2/g, respectively. The phosphate desorption study was conducted on soil samples which received different phosphorous (P) treatments, 0, 50,100 and 150 mg kg−1, for 28 days of desorption time and the phosphate desorption from soil to plant was predicted. The results suggested that the phosphorus treatment and desorption time had significant effect on the amount of desorbed phosphorus. Thus, low (0.71–13.41 mg kg−1) P was desorbed from control and higher (1.87–27.84 mg kg−1) P was desorbed from soils receiving the highest P doze (150 mg kg−1) at all levels of extraction time (1–28 days) for all soil samples. The rate of desorption of P through DMT was found to be 0.0271 hr−1 and was low as compared to other findings which implies the soil samples in this study were highly acidic with high phosphorus fixing property. Generally, the present study attempts to add insight on the potential of this method for assessing phosphate desorption kinetics from acidic soil, relevant for agronomic and environmental advising of phosphate fertilizer application and use.