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Single‐walled carbon nanotubes (CNTs) are carbon materials with unique thermal, optical, mechanical, and electrical properties, with hollow cylindrical structures of a few nanometers in diameter. CNTs cut to about 10 nm (Ultrashort CNTs, US‐CNTs) can spontaneously insert into lipid bilayers. Therefore, applications have been proposed to combine CNTs with lipid bilayers to give the membranes the properties of CNTs. However, CNTs interact with membranes to induce morphological changes in the membranes, which may hinder these applications. In this study, to investigate the effects, US‐CNTs are exposed to lipid bilayer vesicles (giant unilamellar vesicles, GUVs), which are used as a model for cell membranes, and the changes in membrane morphology with each US‐CNT concentration were evaluated by fluorescence microscopy. As a result, GUVs show morphological changes upon exposure to US‐CNTs, eventually transforming into a multiple vesicle‐linked shape. This result suggests an increase in the area and asymmetry of the GUV membrane. Based on these results, we have proposed a hypothesis regarding the mechanism of morphological changes induced in the GUV membranes by US‐CNTs exposure. [ABSTRACT FROM AUTHOR]

Lipid bilayer membranes such as liposomes have been utilized as platforms for bioinspired artificial photosynthesis. Embedding functional compounds, including chromophores and catalysts, into two‐dimensional lipid membranes allows their high local concentration and proximity, resulting in enhanced reactivity compared to that of homogeneous solutions. The control of photoreactions by the physical and chemical properties of membranes, such as fluidity and phase separation, has also been well studied in recent years. In contrast, it remains difficult to control chemical reactions via dynamic membrane deformation. Here, we report on the control of excitation energy transfer using red blood cell ghosts (RBCGs) as scaffolds, relying on their asymmetric lipid membranes and inherent and unique deformability. RBCGs, in which donor and acceptor molecules were chemically conjugated to a two‐dimensional cytoskeleton located beneath the inner membrane, exhibited energy transfer, and their efficiency varied depending on the amount and ratio of donor and acceptor modifications, as confirmed by experimental and theoretical analysis. Furthermore, the KCl concentration‐induced RBCG shrinkage enhanced the energy transfer efficiency. Our proposed method is expected to facilitate the construction of photoreaction systems that can be controlled via membrane deformation. [ABSTRACT FROM AUTHOR]

Aim of the study was to prove the possibility of using red blood cell probe microscopy as a predictor of the development of pancreonecrosis.Material and methods. Atomic force microscopy was performed in 143 people (82 were male and 61 were female). The study was performed on an Integra Aura probe microscope (ZAO NT-MDT, Russia). Each erythrocyte was scanned for cell membrane and cell as a whole. A total of 940 red blood cells were examined. According to the severity of acute pancreatitis, patients are distributed in three groups. As a control group, 37 people without somatic pathology were examined. Diagnosis and treatment of patients was carried out in the public health institution “Design Bureau” Russian Railways-Medicine “Krasnoyarsk” from 2015–2019.Results. The study showed that the shape of erythrocyte does not depend on the severity of pancreatitis and does not change, however, structural changes of the membrane occur in the form of the formation of multiple erosions on its surface. The membrane is deformed, and its adhesion increases. These changes reduce the transport capacity of the blood, which, in our opinion, leads to an increase in the general intoxication of the body and to a deterioration in the condition of the patient.Conclusions. Apparently, pancreatic enzymes entering the free bloodstream in the first phase of pancreatitis cause not only oxidative stress, but also the reorganization and destruction of the erythrocyte membrane. The increase in membrane rigidity and deformation of the erythrocyte surface cytoskeleton against the background of increased adhesion seems to disrupt the gas transmission function of erythrocyte and microrheological properties of blood, which in turn disrupts the exchange of amino acids, lipids and detoxification capabilities of blood. The appearance of erythrocytes in the free bloodstream with the presence of erosion on the surface of the erythrocyte membrane can serve as a prediction of a non-favorable course of acute pancreatitis and a predictor of a possible transition of edema pancreatitis to pancreonecrosis.

As a short-process hydrometallurgical technology, slurry electrolysis (SE) collects the stirring that improves the suspension of ore, the membrane bag that acts as purifying, and the cathodic and anodic plates that promote ion migration in one tank. The stirring helps to maintain the ore suspended. As the SE tank is stirred, the membrane bag will deform and become damaged, severely limiting production efficiency. In this research, the one-way fluid-structure interaction (FSI) was used to examine the impact of the solid–liquid suspension on membrane deformation, which was based on the computational fluid dynamics (CFD) and solid finite element method (FEM). Through the full 3D quantitative analysis, the database of membrane deformation under various conditions was established. The membrane was extruded to the center during the initial stirring conditions, and the greatest deformation measured 891.66 mm. Primarily, membrane deformation was brought on by the pressure differential brought on by liquid velocity, solid concentration distribution, and liquid level. The maximum deformation of the membrane first decreased and then increased with the increased liquid level difference between the cathode and anode. With the upper fixed constraint, the maximum deformation of the membrane appears at y = 1.2 m. The larger the stirring speed is, the smaller the optimal liquid level difference required to minimize the membrane deformation. The stirring speed changes the overall pressure distribution by changing the dynamic pressure in the anode domain. The maximum deformation of the membrane decreases first and then increases with the increase of electrolyte density in the cathode domain. The membrane bag is extruded to the cathode domain when the pressure in the cathode region is insufficient because of the low electrolyte density in the cathode domain. When the cathode pressure increases, the membrane bag bulges to both sides, and the inner bulge is greater than the outer. With an increase in solid volume concentration (SL) in the anode domain, the maximum membrane deformation first reduces and subsequently increases. When SL = 15%, the membrane deformation reaches the minimum value of 226.7 mm. The closer to the bottom of the tank, the greater the influence of solid content on absolute pressure. The maximum membrane deformation is drastically decreased to 0.664 mm when the frame restrictions are considered. It can support the industrial control process via visual analysis.

As an alternative to antibiotics, Antimicrobial Peptides (AMPs) possess unique properties including cationic, amphipathic and their abundance in nature, but the exact characteristics of AMPs against bacterial membranes are still undetermined. To estimate the structural stability and functional activity of AMPs, the Pseudin AMPs (Pse-1, Pse-2, Pse-3, and Pse-4) from Hylid frog species, Pseudis paradoxa, an abundantly discovered source for AMPs were examined. We studied the intra-peptide interactions and thermal denaturation stability of peptides, as well as the geometrical parameters and secondary structure profiles of their conformational trajectories. On this basis, the peptides were screened out and the highly stable peptide, Pse-4 was subjected to membrane simulation in order to observe the changes in membrane curvature formed by Pse-4 insertion. Monomeric Pse-4 was found to initiate the membrane disruption; however, a stable multimeric form of Pse-4 might be competent to counterbalance the helix-coil transition and to resist the hydrophobic membrane environment. Eventually, hexameric Pse-4 on membrane simulation exhibited the hydrogen bond formation with E. coli bacterial membrane and thereby, leading to the formation of membrane spanning pore that allowed the entry of excess water molecules into the membrane shell, thus causing membrane deformation. Our report points out the mechanism of Pse-4 peptide against the bacterial membrane for the first time. Relatively, Pse-4 works on the barrel stave model against E. coli bacterial membrane; hence it might act as a good therapeutic scaffold in the treatment of multi-drug resistant bacterial strains. [ABSTRACT FROM AUTHOR]

In 2020, the pandemic interrupted the series of biannual International Neuroacanthocytosis Meetings that brought together clinicians, scientists, and patient groups to share research into a small group of devastating genetic diseases that combine both acanthocytosis (deformed red blood cells) and neurodegeneration with movement disorders. This Meeting Report describes talks at the 5th VPS13 Forum in January 2022, one of a series of online meetings held to fill the gap. The meeting addressed the basic biology of two key proteins implicated in chorea-acanthocytosis (mutations in VPS13A) and McLeod syndrome (mutations in XK). In a remarkable confluence of ideas, the speakers described different aspects of a single functional unit that comprises of VPS13A and XK proteins working together. Conditions caused by VPS13 (A-D) gene family mutations and related genes, such as XK, previously footnote knowledge, seem to turn central for a novel disease paradigm: bulk lipid transfer disorders. [ABSTRACT FROM AUTHOR]

In reverse osmosis spiral wound membrane modules, the applied pressure causes membrane intrusion in permeate channels, altering the permeate flow. The present study developed a 3-D mechanical and fluid dynamics simulation framework, applied at the small scale of a periodic unit of membrane-permeate spacer assembly. The feed spacer was not simulated and only one membrane placed above the permeate spacer was analysed (one-sided intruding system, like in the used experimental flow cell). The mechanical model computed the deformation of the assembly under different pressures, taking an undeformed spacer geometry accurately determined by CT scanning. Detailed deformed permeate channel configurations were obtained. The mechanical characteristics of the membrane and permeate spacer were estimated by making use of membrane intrusion experimental data obtained by microscopic quantitative imaging with optical coherence tomography. The computed deformed membrane-spacer geometries were used in fluid dynamics calculations. An excellent agreement was found between numerical and experimental data on pressure drop versus velocity in deformed channels. The membrane intrusion under pressure caused a large reduction in permeate channel porosity and thus a strong increase of pressure loss. This study reveals the importance of considering mechanical deformations in computing performance indicators while designing pressure-based membrane separation modules. [Display omitted] • Coupling mechanical and hydrodynamic 3-D modelling at various applied pressures • Detailed 3-D deformed permeate channel configurations were obtained. • In-situ OCT scanning provided experimental membrane deformation. • Mechanical properties estimated by comparing model results with quantitative imaging. • Permeate flow pressure drop well predicted by CFD on detailed deformed geometries. [ABSTRACT FROM AUTHOR]

Biological membranes are complex and dynamic structures with different populations of lipids in their inner and outer leaflets. The Ca 2+ -activated TMEM16 family of membrane proteins plays an important role in collapsing this asymmetric lipid distribution by spontaneously, and bidirectionally, scrambling phospholipids between the two leaflets, which can initiate signaling and alter the physical properties of the membrane. While evidence shows that lipid scrambling can occur via an open hydrophilic pathway ("groove") that spans the membrane, it remains unclear if all family members facilitate lipid movement in this manner. Here we present a comprehensive computational study of lipid scrambling by all TMEM16 members with experimentally solved structures. We performed coarse-grained molecular dynamics (MD) simulations of 27 structures from five different family members solved under activating and non-activating conditions, and we captured over 700 scrambling events in aggregate. This enabled us to directly compare scrambling rates, mechanisms, and protein-lipid interactions for fungal and mammalian TMEM16s, in both open (Ca 2+ -bound) and closed (Ca 2+ -free) conformations with statistical rigor. We show that all TMEM16 structures thin the membrane and that the majority of (>90%) scrambling occurs at the groove only when TM4 and TM6 have sufficiently separated. Surprisingly, we also observed 60 scrambling events that occurred outside the canonical groove, over 90% of which took place at the dimer-dimer interface in mammalian TMEM16s. This new site suggests an alternative mechanism for lipid scrambling in the absence of an open groove., Impact Statement: The majority of TMEM16 lipid scrambling occurs in the open groove associated with Ca 2+ -activation, but limited scrambling also occurs in the dimer interface independent of Ca 2+ .

Establishment of interactions with the envelope lipids is a cardinal feature of broadly neutralizing antibodies (bnAbs) that recognize the Env membrane-proximal external region (MPER) of HIV. The lipid envelope constitutes a relevant component of the full "quinary" MPER epitope, and thus antibodies may be optimized through engineering their capacity to interact with lipids. However, the role of the chemically complex lipid nanoenvironment in the mechanism of MPER molecular recognition and viral neutralization remains poorly understood. To approach this issue, we computationally and experimentally investigated lipid interactions of broadly neutralizing antibody 10E8 and optimized versions engineered to enhance their epitope and membrane affinity by grafting bulky aromatic compounds. Our data revealed a correlation between neutralization potency and the establishment of favorable interactions with small headgroup lipids cholesterol and phosphatidylethanolamine, evolving after specific engagement with MPER. Molecular dynamics simulations of chemically modified Fabs in complex with an MPER-Transmembrane Domain helix supported the generation of a nanoenvironment causing localized deformation of the thick, rigid viral membrane and identified sphingomyelin preferentially occupying a phospholipid-binding site of 10E8. Together, these interactions appear to facilitate insertion of the Fabs through their engagement with the MPER epitope. These findings implicate individual lipid molecules in the neutralization function of MPER bnAbs, validate targeted chemical modification as a method to optimize MPER antibodies, and suggest pathways for MPER peptide-liposome vaccine development.

Liposomes are widely utilized in therapeutic nanosystems as promising drug carriers for cancer treatment, which requires a meticulous synthesis approach to control the nanoprecipitation process. Acoustofluidic platforms offer a favorable synthesis environment by providing robust agitation and rapid mixing. Here, a novel high-throughput acoustofluidic micromixer is presented for a solvent and solvent-free synthesis of ultra-small and size-tunable liposomes. The size-tunability is achieved by incorporating glycerol as a new technique into the synthesis reagents, serving as a size regulator. The proposed device utilizes the synergistic effects of vibrating trapped microbubbles and an oscillating thin elastic membrane to generate vigorous acoustic microstreaming. The working principle and mixing mechanism of the device are explored numerically and experimentally. The platform exhibits remarkable mixing efficacy for aqueous and viscous solutions at flow rates up to 8000 µL/h, which makes it unique for high-throughput liposome formation and preventing aggregation. As a proof of concept, this study investigates the impact of phospholipid type and concentration, flow rate, and glycerol on the size and size distribution of liposomes. The results reveal a significant size reduction, from ≈900 nm to 40 nm, achieved by merely introducing 75% glycerol into the synthesis reagents, highlighting an innovative approach toward size-tunable liposomes., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Deformation of the membrane can seriously hamper the performance of a reverse osmosis process. Currently, the most used approach to obtain detailed information on membrane deformation is by conducting membrane autopsy. However, ex-situ analysis can only observe irreversible deformation. In this study, optical coherence tomography (OCT) was introduced as method for in-situ 3D visualization and quantification of membrane and feed channel deformation during operation with varying transmembrane pressure (0–55 bar). In-situ monitoring of membrane surface geometry in a lab-scale flow-cell revealed the formation of specific patterns with ridges and valleys. The deformation became more pronounced with increasing applied pressure, due to membrane intrusion into the permeate spacer. The asymmetric structure of the permeate spacer causes a clear distinction in spatial distribution of ridges and valleys, depending on which side faces the membrane. Interestingly, membrane surface displacement increased linearly with TMP, with slope depending on spacer orientation (A vs B) and type (BW vs SW). Under pressure, we found the following displacements: Ridge – BW-A 1.7 ± 0.1 μm/bar, BW-B 1.9 ± 0.1 μm/bar, SW-A&B 1.5 ± 0.3 μm/bar; Valley – BW-A 3.2 ± 0.1 μm/bar, BW-B 2.7 ± 0.1 μm/bar, SW-A 1.7 ± 0.2 μm/bar, SW-B 1.8 ± 0.3 μm/bar. Measuring the membrane position under pressure revealed that the displacement involves the whole membrane-permeate spacer structure, i.e., the permeate spacer is also deformed. By alternating high and low feed pressure, we could distinguish between reversible and irreversible deformation. In-situ measurement of membrane deformation can contribute to understanding of pressure related performance and can serve as input for advanced modeling. [Display omitted] • OCT enables in-situ quantification and visualization of RO membrane deformation. • Membrane deformation correlates approximately linearly with transmembrane pressure. • Membrane deformation under operating pressure is partially reversible. [ABSTRACT FROM AUTHOR]

[Display omitted] Native lipids in cell-membrane support crucial functions like intercell communication via their ability to deform into curved membrane structures. Cell membrane mimicking Giant unilamellar vesicles (GUV) is imperative in understanding native lipid's role in membrane transformation however remains challenging to assemble. We construct two giant vesicle models mimicking bacterial inner-membrane (IM) and outer-membrane (OM) under physiological conditions using single-step gel-assisted lipid swelling. IM vesicles composed of native bacterial lipids undergo small-scale membrane remodeling into bud and short-nanotube structures. In contrast, OM vesicles asymmetrically assembled from Lipopolysaccharide (LPS) and bacterial lipids underwent global membrane deformation under controlled osmotic stress. Remarkably, highly-curved structures mimicking cell-membrane architectures, including daughter vesicle networks interconnected by necks and nano-tubes ranging from micro to nanoscale, are generated in OM vesicles at osmotic stress comparable to that applied in IM vesicles. Further, we provide a quantitative description of the membrane structures by experimentally determining membrane elastic parameters, i.e., neck curvature and bending rigidity. We can conclude that a larger spontaneous curvature estimated from the neck curvature and softer membranes in OM vesicles is responsible for large-scale deformation compared to IM vesicles. Our findings will help comprehend the shape dynamics of complex native bacterial lipid membranes. [ABSTRACT FROM AUTHOR]

Nonenveloped viruses employ unique entry mechanisms to breach and infect host cells. Understanding these mechanisms is crucial for developing antiviral strategies. Prevailing perspective suggests that nonenveloped viruses release membrane pore-forming peptides to breach host membranes. However, the precise involvement of the viral capsid in this entry remains elusive. Our study presents direct observations elucidating the dynamically distinctive steps through which metastable reovirus capsids disrupt host lipid membranes as they uncoat into partially hydrophobic intermediate particles. Using both live cells and model membrane systems, our key finding is that reovirus capsids actively deform and permeabilize lipid membranes in a cholesterol-dependent process. Unlike membrane pore-forming peptides, these metastable viral capsids induce more extensive membrane perturbations, including budding, bridging between adjacent membranes, and complete rupture. Notably, cholesterol enhances subviral particle adsorption, resulting in the formation of pores equivalent to the capsid size. This cholesterol dependence is attributed to the lipid condensing effect, particularly prominent at an intermediate cholesterol level. Furthermore, our results reveal a positive correlation between membrane disruption extent and efficiency of viral variants in establishing infection. This study unveils the crucial role of capsid-lipid interaction in nonenveloped virus entry, providing new insights into how cholesterol homeostasis influences virus infection dynamics.

During the blood stage of malaria pathogenesis, parasites invade healthy red blood cells (RBC) to multiply inside the host and evade the immune response. When attached to RBC, the parasite first has to align its apex with the membrane for a successful invasion. Since the parasite’s apex sits at the pointed end of an oval (egg-like) shape with a large local curvature, apical alignment is in general an energetically unfavorable process. Previously, using coarse-grained mesoscopic simulations, we have shown that optimal alignment time is achieved due to RBC membrane deformation and the stochastic nature of bond-based interactions between the parasite and RBC membrane (Hillringhaus et al., 2020). Here, we demonstrate that the parasite’s shape has a prominent effect on the alignment process. The alignment times of spherical parasites for intermediate and large bond off-rates (or weak membrane-parasite interactions) are found to be close to those of an egg-like shape. However, for small bond off-rates (or strong adhesion and large membrane deformations), the alignment time for a spherical shape increases drastically. Parasite shapes with large aspect ratios such as oblate and long prolate ellipsoids are found to exhibit very long alignment times in comparison to the egg-like shape. At a stiffened RBC, a spherical parasite aligns faster than any other investigated shape. This study shows that the original egg-like shape performs not worse for parasite alignment than other considered shapes but is more robust with respect to different adhesion interactions and RBC membrane rigidities.

Motility and membrane deformation are crucial to motile cells. Therefore formation of protrusion in the membrane has been the subject of various studies. The stable shape of the membrane and also its movements are controlled by the forces exerted by actin filaments. In order to study the protrusion behavior, we represented a toy model based on actin filaments polar characteristic and elastic characteristic of the membrane. We also studied the effect of changing physical parameters such as filament density, the membrane tension, and the polymerization rate on the shape and the magnitude of the protrusion.

The deformation of the solar-sail membrane is an important factor for causing inaccuracies in the solar-sail missions. This paper describes the solar sail under deformation by using a new modelling technique based on point cloud and triangular mesh generation. Two types of deformation, stemming from wrinkling and billowing, are modelled. The changes in the solar radiation pressure force and the moment caused by deformation are calculated and compared to the ideal non-deformed case. The heliocentric spiral trajectory and the orbital angular momentum reversal trajectory are taken as examples to quantify the influence of the deformation from an orbit point of view. Additionally, point cloud simplification, based on the normal vector and bounding box, is utilized to simplify the original deformed-sail model. It involves a reasonable reduction and renewal of the points in the model considering the variation of surface curvature. The simplification and its modelling accuracy are numerically investigated as well as computational efficiency. [ABSTRACT FROM AUTHOR]

The sorting nexin (SNX) family of proteins deform the membrane to generate transport carriers in endosomal pathways. Here, we elucidate how a prototypic member, SNX1, acts in this process. Performing cryoelectron microscopy, we find that SNX1 assembles into a protein lattice that consists of helical rows of SNX1 dimers wrapped around tubular membranes in a crosslinked fashion. We also visualize the details of this structure, which provides a molecular understanding of how various parts of SNX1 contribute to its ability to deform the membrane. Moreover, we have compared the SNX1 structure with a previously elucidated structure of an endosomal coat complex formed by retromer coupled to a SNX, which reveals how the molecular organization of the SNX in this coat complex is affected by retromer. The comparison also suggests insight into intermediary stages of assembly that results in the formation of the retromer-SNX coat complex on the membrane. [ABSTRACT FROM AUTHOR]

Vesicle structures primarily embody spherical capsules composed of a single or multiple bilayers, entrapping a pool of aqueous solution in their interior. The bilayers can be synthesised by phospholipids or other amphiphiles (surfactants, block copolymers, etc.). Vesicles with broad-spectrum applications in numerous scientific disciplines, including biochemistry, biophysics, biology, and various pharmaceutical industries, have attracted widespread attention. Consequently, a multitude of protocols have been devised and proposed for their fabrication. In this review, with a motivation to derive the basic conditions for the formation of vesicles, the associated thermodynamic and kinetic aspects are comprehensively appraised. Contextually, an all-purpose overview of the underlying thermodynamics of bilayer/membrane generation and deformation, including the chemical potential of aggregates, geometric packing and the concept of elastic properties, is presented. Additionally, the current review highlights the probable, inherent mechanisms of vesicle formation under distinct modes of manufacturing. We lay focus on vesicle formation from pre-existing bilayers, as well as from bilayers, which form when lipids from an organic solvent are transferred into an aqueous medium. Furthermore, we outline the kinetic effects on vesicle formation from the lamellar phase, with and without the presence of shearing force. Wherever required, the experimental and/or theoretical outcomes, the driving forces for vesicle size selection, and various scaling laws are also reviewed, all of which facilitate an overall improved understanding of the vesicle formation mechanisms. [ABSTRACT FROM AUTHOR]

Membranes are the key structures to separate and spatially organize cellular systems. Their rich dynamics and transformations during the cell cycle are orchestrated by specific membrane-targeted molecular machineries, many of which operate through energy dissipation. Likewise, man-made light-activated molecular rotary motors have previously shown drastic effects on cellular systems, but their physical roles on and within lipid membranes remain largely unexplored. Here, the impact of rotary motors on well-defined biological membranes is systematically investigated. Notably, dramatic mechanical transformations are observed in these systems upon motor irradiation, indicative of motor-induced membrane expansion. The influence of several factors on this phenomenon is systematically explored, such as motor concentration and membrane composition., Membrane fluidity is found to play a crucial role in motor-induced deformations, while only minor contributions from local heating and singlet oxygen generation are observed. Most remarkably, the membrane area expansion under the influence of the motors continues as long as irradiation is maintained, and the system stays out-of-equilibrium. Overall, this research contributes to a comprehensive understanding of molecular motors interacting with biological membranes, elucidating the multifaceted factors that govern membrane responses and shape transitions in the presence of these remarkable molecular machines, thereby supporting their future applications in chemical biology., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Depending on the physical and biochemical properties of actin-binding proteins, actin networks form different types of membrane protrusions at the cell periphery. Actin crosslinkers, which facilitate the interaction of actin filaments with one another, are pivotal in determining the mechanical properties and protrusive behavior of actin networks. Short crosslinkers such as fascin bundle F-actin to form rigid spiky filopodial protrusions. By encapsulation of fascin and actin in giant unilamellar vesicles (GUVs), we show that fascin-actin bundles cause various GUV shape changes by forming bundle networks or straight single bundles depending on GUV size and fascin concentration. We also show that the presence of a long crosslinker, α-actinin, impacts fascin-induced GUV shape changes and significantly impairs the formation of filopodia-like protrusions. Actin bundle-induced GUV shape changes are confirmed by light-induced disassembly of actin bundles leading to the reversal of GUV shape. Our study contributes to advancing the design of shape-changing minimal cells for better characterization of the interaction between lipid bilayer membranes and actin cytoskeleton.

Heterogeneities (e.g., membrane proteins and lipid domains) and deformations (e.g., highly curved membrane regions) in biological lipid membranes cause lipid packing defects that may trigger functional sorting of lipids and membrane-associated proteins. To study these phenomena in a controlled and efficient way within molecular simulations, we developed an external field protocol that artificially enhances packing defects in lipid membranes by enforcing local thinning of a flat membrane region. For varying lipid compositions, we observed strong thinning-induced depletion or enrichment, depending on the lipid's intrinsic shape and its effect on a membrane's elastic modulus. In particular, polyunsaturated and lysolipids are strongly attracted to regions high in packing defects, whereas phosphatidylethanolamine (PE) lipids and cholesterol are strongly repelled from it. Our results indicate that externally imposed changes in membrane thickness, area, and curvature are underpinned by shared membrane elastic principles. The observed sorting toward the thinner membrane region is in line with the sorting expected for a positively curved membrane region. Furthermore, we have demonstrated that the amphipathic lipid packing sensor (ALPS) protein motif, a known curvature and packing defect sensor, is effectively attracted to thinner membrane regions. By extracting the force that drives amphipathic molecules toward the thinner region, our thinning protocol can directly quantify and score the lipid packing sensing of different amphipathic molecules. In this way, our protocol paves the way toward high-throughput exploration of potential defect- and curvature-sensing motifs, making it a valuable addition to the molecular simulation toolbox.

S-acylation, whereby a fatty acid chain is covalently linked to a cysteine residue by a thioester linkage, is the most prevalent kind of lipid modification of proteins. Thousands of proteins are targets of this post-translational modification, which is catalyzed by a family of eukaryotic integral membrane enzymes known as DHHC protein acyltransferases (DHHC-PATs). Our knowledge of the repertoire of S-acylated proteins has been rapidly expanding owing to development of the chemoproteomic techniques. There has also been an increasing number of reports in the literature documenting the importance of S-acylation in human physiology and disease. Recently, the first atomic structures of two different DHHC-PATs were determined using X-ray crystallography. This review will focus on the insights gained into the molecular mechanism of DHHC-PATs from these structures and highlight representative data from the biochemical literature that they help explain. Unlabelled Image • Protein S-acylation is one of the most abundant forms of protein lipidation. • Members of the DHHC family of integral membrane enzymes catalyze protein S-acylation in eukaryotes. • High-resolution structures of two members of the family revealed a tremendous amount of information about organization and mechanism of DHHC enzymes. • Atomistic molecular dynamics simulation revealed DHHC enzymes deform the membrane to facilitate catalysis. [ABSTRACT FROM AUTHOR]

Heterogeneities (e.g., membrane proteins and lipid domains) and deformations (e.g., highly curved membrane regions) in biological lipid membranes cause lipid packing defects that may trigger functional sorting of lipids and membrane-associated proteins. To study these phenomena in a controlled and efficient way within molecular simulations, we developed an external field protocol that artificially enhances packing defects in lipid membranes by enforcing local thinning of a flat membrane region. For varying lipid compositions, we observed strong thinning-induced depletion or enrichment, depending on the lipid's intrinsic shape and its effect on a membrane's elastic modulus. In particular, polyunsaturated and lysolipids are strongly attracted to regions high in packing defects, whereas phosphatidylethanolamine (PE) lipids and cholesterol are strongly repelled from it. Our results indicate that externally imposed changes in membrane thickness, area, and curvature are underpinned by shared membrane elastic principles. The observed sorting toward the thinner membrane region is in line with the sorting expected for a positively curved membrane region. Furthermore, we have demonstrated that the amphipathic lipid packing sensor (ALPS) protein motif, a known curvature and packing defect sensor, is effectively attracted to thinner membrane regions. By extracting the force that drives amphipathic molecules toward the thinner region, our thinning protocol can directly quantify and score the lipid packing sensing of different amphipathic molecules. In this way, our protocol paves the way toward high-throughput exploration of potential defect- and curvature-sensing motifs, making it a valuable addition to the molecular simulation toolbox. [ABSTRACT FROM AUTHOR]

Catestatin (CST), a versatile 21 amino acid long cationic peptide, is stored in chromaffin granules and exocytosed upon fusion with the plasma membrane. CST, produced by chromaffin cells and neutrophils, is derived from the processing of chromogranin A and induced in the skin after injury. It involves catecholamine inhibition, blood pressure control, inflammation, and innate immunity. It is thought that calcium influx is triggered by CST permeating within neutrophils. It is unknown whether CST can disturb the immediate environment enough to penetrate the cell membrane passively. We used molecular dynamics simulations to examine the behaviour of human CST in its wild-type state (CST WT) and one of its naturally occurring variants, CST-364 S, which has a high allelic frequency in the human population. Both peptides were incorporated into the model eukaryotic cell membrane known as the POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine) lipid bilayer. The molecular modelling and simulations results show that CST WT and CST-364 S have different propensities for membrane disruption. It was shown that CST-364 S has higher membrane permeability than CST WT. In addition, we have used fluorescence anisotropy and leakage assay to study the interaction of peptides with PC membranes. Both peptides interacted with POPC and DOPC membranes, while CST-364 S penetrated the membrane more deeply via disorganizing the membrane interface, which supports our previous findings. According to this study, there is a good possibility that the peptides will passively permeate the cell membrane, distort, and pass through it. [Display omitted] • Catestatin (CST) inhibits catecholamine, regulates blood pressure, inflammation, & immunity. • MD simulations analysis of human CST –wild type and its high allelic frequency CST-364 S variant • Both peptides were incorporated into the model eukaryotic cell membrane POPC lipid bilayer. • Different membrane disruption propensities by two variants, CST-364 S shows higher permeability. • Fluorescence anisotropy and leakage assay for the interaction of peptides with PC membranes [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated the crucial role of cholesterol (Chol) in regulating the mechanical properties and biological functions of cell membranes. Methyl-β-cyclodextrin (MeβCD) is commonly utilized to modulate the Chol content in cell membranes, but there remains a lack of a comprehensive understanding. In this study, using a range of different techniques, we find that the optimal ratio of MeβCD to Chol for complete removal of Chol from a phosphocholine (PC)/Chol mixed membrane with a 1:1 mol ratio is 4.5:1, while the critical MeβCD-to-Chol ratio for membrane permeation falls within the range between 1.5 and 2.4. MeβCD at elevated concentrations induces the formation of fibrils or tubes from a PC membrane. Single lipid tracking reveals that removing Chol restores the diffusion of lipid molecules in the PC/Chol membrane to levels observed in pure PC membranes. Exposure to 5 mM MeβCD for 30 min effectively eliminates Chol from various cell lines, leading to an up to 8-fold enhancement in melittin cytotoxicity over Hela cells and an up to 3.5-fold augmentation of T cell cytotoxicity against B16F10-OVA cells. This study presents a diagram that delineates the concentration- and time-dependent distribution of MeβCD-induced Chol depletion and membrane deformation, which holds significant potential for modulating the mechanical properties of cellular membranes in prospective biomedical applications.

Antimicrobial resistance is a pressing global health issue, with millions of lives at risk by 2050, necessitating the development of alternatives with broad-spectrum activity against pathogenic microbes. Antimicrobial peptides provide a promising solution by combating microbes, modulating immunity, and reducing resistance development through membrane and intracellular targeting. PuroA, a synthetic peptide derived from the tryptophan-rich domain of puroindoline A, exhibits potent antimicrobial activity against various pathogens, while the rationally designed P1 peptide demonstrates enhanced antimicrobial activity with its specific composition. This paper investigates the concentration-dependent effects of these cationic peptides on distinct types of vesicles representing strong-negative bacterial cell membranes (S-vesicles), weak-negative bacterial cell membranes (W-vesicles), and mammalian cell membranes (M-vesicles). To investigate the interactions between the peptides and vesicles, small-angle neutron scattering experiments were conducted. The cationic peptides, PuroA and P1, interact with S-vesicles through electrostatic interactions, leading to distinct effects. PuroA accumulates on the vesicle surface, increasing R core and R total , aligning with the carpet model. P1 disrupts the vesicle structure at higher concentrations, consistent with the detergent model. Neither peptide significantly affects W-vesicles, emphasizing the role of charge. In uncharged M-vesicles, both peptides decrease R core and R total and increase t shell , indicating peptide insertion and altered bilayer properties. These findings provide valuable insights into peptide-membrane interactions and their impact on vesicle structures. Furthermore, the implications of these findings extend to the potential development of innovative antimicrobial agents and drug delivery systems that specifically target bacterial and mammalian membranes. This research contributes to the advancement of understanding peptide-membrane interactions and lays the foundation for the design of approaches for targeting membranes in various biomedical applications.

Molecules interfering with lipid bilayer function exhibit strong antiviral activity against a broad range of enveloped viruses, with a lower risk of resistance development than that for viral protein-targeting drugs. Amphipathic peptides are rich sources of such membrane-interacting antivirals. Here, we report that influenza viruses were effectively inactivated by M2 AH, an amphipathic peptide derived from the M2 protein of the influenza virus. Although overall hydrophobicity () of M2 AH was not related to antiviral activity, modification of the hydrophobic moment (<μH>) of M2 AH dramatically altered the antiviral activity of this peptide. M2 MH, a derivative of M2 AH with a <μH> of 0.874, showed a half maximal inhibitory concentration (IC 50) of 53.3 nM against the A/PR/8/34 strain (H1N1), which is 16-times lower than that of M2 AH. The selectivity index (IC 50 /CC 50), where CC 50 is the half maximal cytotoxic concentration, was 360 for M2 MH and 81 for M2 AH. Dynamic light scattering spectroscopy and electron microscopy revealed that M2 AH-derived peptides did not disrupt liposomes but altered the shape of viruses. This result suggests that the shape of virus envelope was closely related to its activity. Thus, we propose that deforming without rupturing the membranes may achieve a high selectivity index for peptide antivirals. • M2 AH is an amphipathic peptide derived from influenza virus M2 protein. • M2 MH with elevated hydrophobic moment was a strong antiviral with low toxicity. • M2 AH and MH did not disrupt membrane but simply deformed the shape of virus. • Deformation of viral envelope may achieve a high selectivity index for peptide antivirals. [ABSTRACT FROM AUTHOR]

An inflatable aerodynamic decelerator with a membrane aeroshell is a promising key technology in the reentry, descent, and landing phases of future space transportation. The membrane aeroshell is generally deformed by the in-flight aerodynamic force; however, the effects of the deformation on the aerodynamic heating are unclear. Here, we investigated aerodynamic heating for an inflatable reentry vehicle, Titans, in the hypersonic regime using flow field simulation coupled with structural analysis. Thermochemical nonequilibrium flows around the Titans with a deformed membrane aeroshell were reproduced numerically for an angle of attack (AoA) values between 0° and 40°. The maximum displacements of the membrane aeroshell by deformation at the AoAs of 0° and 40° were 6.7% and 6.6% of the diameter of the Titans, respectively. The difference in heat fluxes between the deformed and rigid shapes was a remarkable 188.8% for a 0° AoA owing to the considerable changes in the front shock wave shape. Meanwhile, it was indicated that membrane deformation at an AoA of 40° insignificantly affected the peak heat flux value on the inflatable torus because the considerable change in the shock wave shape observed for the case of 0° AoA did not occur. It was found that local wrinkles on the membrane aeroshell were formed by deformation, thus causing the heat flux to increase owing to an increase in local temperature gradient on the surface. [ABSTRACT FROM AUTHOR]

Abstract Pressure-retarded membrane distillation (PRMD) is an emerging membrane process to recover energy from low-grade heat sources. The applied hydraulic pressure on the cold-water side in PRMD may strongly affect both energy conversion efficiency and membrane performance. Here, we report the first systematic study on this critical issue. A commercial nanoporous polytetrafluoroethylene membrane was evaluated as a general membrane sample over a range of applied pressures from 0 to 10 bar at a temperature difference of 40 °C. Our results show that the theoretically projected constant water vapor flux decreases significantly with the increase of the applied pressures, which can be attributed to the severe membrane deformation induced by pressures. The membrane in the active-layer-facing-hot-solution orientation is mechanically unstable with the complete loss of water vapor flux under 2 bar. In contrast, the membrane in the active-layer-facing-cold-solution orientation can still work under 10 bar. Combining theoretical analysis and detailed characterization of membrane physical structures, we show that the properties of membrane active layers (i.e. , pore size, porosity, and thickness) deteriorate under elevated pressures. Deformed membranes have lower permeability and higher temperature polarization in PRMD, resulting in the observed lower water vapor fluxes. Our results suggest that improving the mechanical stability of membranes would be the first critical step in realizing practical applications of PRMD for low-grade heat recovery. Potential research directions for developing novel PRMD membranes are also proposed. Graphical abstract Image 1 Highlights • Water vapor flux decreases with the increase of applied hydraulic pressure in pressure-retarded membrane distillation for waste heat recovery. • Membranes in the active layer facing cold permeate solution orientation have much better mechanical stability. • Structural properties of the membrane active layer deteriorate under elevated pressures. • The loss in water vapor flux can be attributed to decreased membrane permeability and severe temperature polarization. [ABSTRACT FROM AUTHOR]

The metabolism of PI(3,5)P2 is regulated by the PIKfyve, VAC14 and FIG4 complex, whose mutations are associated with hypopigmentation in mice. These pigmentation defects indicate a key but yet unexplored physiological relevance of this complex in the biogenesis of melanosomes. Here we show that PIKfyve activity regulates formation of amyloid matrix composed of PMEL protein within early endosomes, called stage I melanosomes. PIKfyve activity controls the membrane remodeling of stage I melanosomes that increases PMEL abundance and impairs its sorting and processing. PIKfyve activity also affects stage I melanosome kiss-and-run interactions with lysosomes that is required for PMEL amyloidogenesis and establishment of melanosome identity. Mechanistically, PIKfyve activity promotes the formation and membrane tubules from stage I melanosomes and their release by modulating endosomal actin branching. Together our data indicate that PIKfyve activity is a key regulator of the melanosomal import-export machinery that fine tunes the formation of functional amyloid fibrils in melanosomes and the maintenance of melanosome identity. [ABSTRACT FROM AUTHOR]

Abstract Electroporation-based techniques, i.e. techniques based on the perturbation of the cell membrane through the application of electric pulses, are widely used at present in medicine and biotechnology. However, the electric pulse - cell membrane interaction is not yet completely understood neither explicitly formalized. Here we introduce a Multiphysics (MP) model describing electric pulse - cell membrane interaction consisting on the Poisson equation for the electric field, the Nernst-Planck equations for ion transport (protons, hydroxides, sodium or calcium, and chloride), the Maxwell tensor and mechanical equilibrium equation for membrane deformations (with an explicit discretization of the cell membrane), and the Smoluchowski equation for membrane permeabilization. The MP model predicts that during the application of an electric pulse to a spherical cell an elastic deformation of its membrane takes place affecting the induced transmembrane potential, the pore creation dynamics and the ionic transport. Moreover, the coincidence among maximum membrane deformation, maximum pore aperture, and maximum ion uptake is predicted. Such behavior has been corroborated experimentally by previously published results in red blood and CHO cells as well as in supramolecular lipid vesicles. Highlights • A Multiphysics (MP) model describing electric pulse - cell membrane interaction has been introduced • Model shows that membrane deformation under electric pulse affects transmembrane potential, pore creation and ion transport. • Maximum cell membrane deformation, maximum pore aperture, and maximum ion uptake coincide at the poles of the cell membrane. • Model behavior is corroborated with experiments in red blood and CHO cells as well as in supramolecular lipid vesicles. [ABSTRACT FROM AUTHOR]

Pex11p family proteins are key players in peroxisomal fission, but their molecular mechanisms remains mostly unknown. In the present study, overexpression of Pex11pβ caused substantial vesiculation of peroxisomes in mammalian cells. This vesicle formation was dependent on dynamin-like protein 1 (DLP1) and mitochondrial fission factor (Mff), as knockdown of these proteins diminished peroxisomal fission after Pex11pβ overexpression. The fission-deficient peroxisomes exhibited an elongated morphology, and peroxisomal marker proteins, such as Pex14p or matrix proteins harboring peroxisomal targeting signal 1, were discernible in a segmented staining pattern, like beads on a string. Endogenous Pex11pβ was also distributed a striped pattern, but which was not coincide with Pex14p and PTS1 matrix proteins. Altered morphology of the lipid membrane was observed when recombinant Pex11p proteins were introduced into proteo-liposomes. Constriction of proteo-liposomes was observed under confocal microscopy and electron microscopy, and the reconstituted Pex11pβ protein localized to the membrane constriction site. Introducing point mutations into the N-terminal amphiphathic helix of Pex11pβ strongly reduced peroxisomal fission, and decreased the oligomer formation. These results suggest that Pex11p contributes to the morphogenesis of the peroxisomal membrane, which is required for subsequent fission by DLP1.

Abstract Membrane blebbing, as a mechanism for cells to regulate their internal pressure and membrane tension, is believed to play important roles in processes such as cell migration, spreading and apoptosis. However, the fundamental question of how different blebs interact with each other during their life cycles remains largely unclear. Here, we report a combined theoretical and experimental investigation to examine how the growth and retraction of a cellular bleb are influenced by neighboring blebs as well as the fusion dynamics between them. Specifically, a boundary integral model was developed to describe the shape evolution of cell membrane during the blebbing/retracting process. We showed that a drop in the intracellular pressure will be induced by the formation of a bleb whose retraction then restores the pressure level. Consequently, the volume that a second bleb can reach was predicted to heavily depend on its initial weakened size and the time lag with respect to the first bleb, all in quantitative agreement with our experimental observations. In addition, it was found that as the strength of membrane-cortex adhesion increases, the possible coalescence of two neighboring blebs changes from smooth fusion to abrupt coalescence and eventually to no fusion at all. Phase diagrams summarizing the dependence of such transition on key physical factors, such as the intracellular pressure and bleb separation, were also obtained. [ABSTRACT FROM AUTHOR]

Background Receptor dependent clathrin-mediated endocytosis (CME) is one of the most important endocytic pathways for the internalization of bioparticles into cells. During CME, the ligand-receptor interactions, development of clathrin-coated pit (CCP) and membrane evolution all act together to drive the internalization of bioparticles. In this work, we develop a stochastic computational model to investigate the CME based on the Metropolis Monte Carlo simulations. Methods The model is based on the combination of a stochastic particle binding model with a membrane model. The energetic costs of membrane bending, CCP formation and ligand-receptor interactions are systematically linked together. Results We implement our model to investigate the effects of particle size, ligand density and membrane stiffness on the overall process of CME from the drug delivery perspectives. Consistent with some experiments, our results show that the intermediate particle size and ligand density favor the particle internalization. Moreover, our results show that it is easier for a particle to enter a cell with softer membrane. Conclusions The model presented here is able to provide mechanistic insights into CME and can be readily modified to include other important factors, such as actins. The predictions from the model will aid in the therapeutic design of intracellular/transcellular drug delivery and antiviral interventions. [ABSTRACT FROM AUTHOR]

Abstract: A major goal of nanotechnology and bioengineering is to build artificial nanomachines capable of generating specific membrane curvatures on demand. Inspired by natural membrane‐deforming proteins, we designed DNA‐origami curls that polymerize into nanosprings and show their efficacy in vesicle deformation. DNA‐coated membrane tubules emerge from spherical vesicles when DNA‐origami polymerization or high membrane‐surface coverage occurs. Unlike many previous methods, the DNA self‐assembly‐mediated membrane tubulation eliminates the need for detergents or top‐down manipulation. The DNA‐origami design and deformation conditions have substantial influence on the tubulation efficiency and tube morphology, underscoring the intricate interplay between lipid bilayers and vesicle‐deforming DNA structures. [ABSTRACT FROM AUTHOR]

The potential of a commercial forward osmosis (FO) module to recover water from NEWater brine, an RO retentate, was assessed by taking an innovative approach to obtaining the mass transfer coefficients. The performance comparison of the spiral wound (S-W) FO module with that of the flat sheet laboratory unit suggests that the winding involved in S-W construction can adversely affect performance; the values for the S-W mass transfer coefficients were half of those expected. This first-of-its-kind performance comparison utilised coupons of the membrane and spacers taken from the module. The module was used both in the conventional manner for FO and in the reverse manner with the active layer facing the draw solution. Estimates of membrane parameters and mass transfer coefficients experiments for the two orientations were obtained using pure water, 10 mM and 25 mM NaCl solution on the feed side and 1 M NaCl as draw solution. The fouling potential of NEWater brine per se was found to be low. These are the first results with a S-W module that suggest potential for this niche application; nevertheless the level of the water flux through the S-W module clearly indicates that industrial applications of S-W FO will be constrained to special cases. [ABSTRACT FROM AUTHOR]

Liquid entry pressure (LEP) of membrane is crucial in the process of membrane distillation (MD) to ensure the quality of distillate since the whole operation will be contaminated as soon as the feed liquid starts to penetrate the hydrophobic membrane. Assuming standard condition (i.e., ambient temperature, hydrostatic pressure, etc.), experimental LEP values were inconsistent compared with theoretical LEP, thus rigorous analysis attempt was made to help understanding the wetting phenomena in MD. We first conducted an experiment with LEP device under various temperature of the feed water. Scanning electron microscopy images were taken to visualize the pore size transition and the results were proved with capillary flow porometry of each membrane after the experiments. Effects of different flow rate have also been studied, yet the results showed no significant difference. As a natural result, LEP is temperature dependent; however, other factors which are not reflected in the LEP equation also exist. Experiments show that the wetting at pressure above LEP may not only wet the membrane but also affect membrane properties. Therefore, in the MD process, the importance of preventing wetting exceeds the necessity of recovering after wetting. [ABSTRACT FROM AUTHOR]

The hydrodynamics of electrodialysis and reverse electrodialysis is commonly studied by neglecting membrane deformation caused by transmembrane pressure (TMP). However, large frictional pressure drops and differences in fluid velocity or physical properties in adjacent channels may lead to significant TMP values. In previous works, we conducted one-way coupled structural-CFD simulations at the scale of one periodic unit of a profiled membrane/channel assembly and computed its deformation and frictional characteristics as functions of TMP. In this work, a novel fluid−structure interaction model is presented, which predicts, at the channel pair scale, the changes in flow distribution associated with membrane deformations. The continuity and Darcy equations are solved in two adjacent channels by treating them as porous media and using the previous CFD results to express their hydraulic permeability as a function of the local TMP. Results are presented for square stacks of 0.6-m sides in cross and counter flow at superficial velocities of 1 to 10 cm/s. At low velocities, the corresponding low TMP does not significantly affect the flow distribution. As the velocity increases, the larger membrane deformation causes significant fluid redistribution. In the cross flow, the departure of the local superficial velocity from a mean value of 10 cm/s ranges between −27% and +39%.

The Reverse Osmosis systems which are widely used in seawater and brackish water may have economically advantages but if it is used efficiently during the working of useful membranes life. The organic and the inorganic contaminants which is in the reverse osmosis feed flow occasionally cause the plug of the surface of the membranes. It's encountered soon or later this situation effects the system of the reverse osmosis productivity negatively. The applications which are done in a better way of the pre-treatment and pre-conditioning is not enough to overcome the plug but put back the formation process. It's necessary to clean the membranes with using suitable methods and suitable chemicals to cure the plug. In the present study, it's aimed to evaluate the negative effects of chemicals using in order to clean polyamide membranes and cleaning procedures. Through the aim of the present study, the membranes problems that are inorganic fouling and biofilms cleaning procedures involving polyamide membranes limited values of chemicals are dealt together. As results of evaluations, it's understood that for necessity of efficient cleaning acidic and alkaline chemicals take an important part cause shortening the efficient usage life. [ABSTRACT FROM AUTHOR]

Paramyxoviruses rely on the matrix (M) protein to orchestrate viral assembly and budding at the plasma membrane. Although the mechanistic details remain largely unknown, structural data suggested that M dimers and/or higher-order oligomers may facilitate membrane budding. To gain functional insights, we employed a structure-guided mutagenesis approach to investigate the role of canine distemper virus (CDV) M protein self-assembly in membrane-budding activity. Three six-alanine-block (6A-block) mutants with mutations located at strategic oligomeric positions were initially designed. While the first one includes residues potentially residing at the protomer-protomer interface, the other two display amino acids located within two distal surface-exposed α-helices proposed to be involved in dimerdimer contacts. We further focused on the core of the dimeric interface by mutating asparagine 138 (N138) to several nonconservative amino acids. Cellular localization combined with dimerization and coimmunopurification assays, performed under various denaturing conditions, revealed that all 6A-block mutants were impaired in selfassembly and cell periphery accumulation. These phenotypes correlated with deficiencies in relocating CDV nucleocapsid proteins to the cell periphery and in virus-like particle (VLP) production. Conversely, all M-N138 mutants remained capable of selfassembly, though to various extents, which correlated with proper accumulation and redistribution of nucleocapsid proteins at the plasma membrane. However, membrane deformation and VLP assays indicated that the M-N138 variants exhibiting the most reduced dimerization propensity were also defective in triggering membrane remodeling and budding, despite proper plasma membrane accumulation. Overall, our data provide mechanistic evidence that the efficiency of CDV M dimerization/oligomerization governs both cell periphery localization and membrane-budding activity. IMPORTANCE Despite the availability of effective vaccines, both measles virus (MeV) and canine distemper virus (CDV) still lead to significant human and animal mortality worldwide. It is assumed that postexposure prophylaxis with specific antiviral compounds may synergize with vaccination campaigns to better control ongoing epidemics. Targeting the matrix (M) protein of MeV/CDV is attractive, because M coordinates viral assembly and egress through interaction with multiple cellular and viral components. However, the lack of basic molecular knowledge of how M orchestrates these functions precludes the rational design of antivirals. Here we combined structure-guided mutagenesis with cellular, biochemical and functional assays to investigate a potential correlation between CDV M self-assembly and virus-like particle (VLP) formation. Altogether, our findings provide evidence that stable M dimers at the cell periphery are required to productively trigger VLPs. Such stabilized M dimeric units may facilitate further assembly into robust higher-order oligomers necessary to promote plasma membrane-budding activity. [ABSTRACT FROM AUTHOR]

Autophagic lysosome reformation (ALR) is the terminal step of autophagy and is essential for maintaining lysosome homeostasis during autophagy. During ALR, tubules are extruded from autolysosomes, and small vesicles named proto-lysosomes, which are composed of lysosomal membrane components, are generated from these tubules. Eventually, proto-lysosomes mature into functional lysosomes. In this review, we will summarize recent progress in understanding the regulation, mechanisms and physiological functions of ALR. [ABSTRACT FROM AUTHOR]

In this paper, a simple and feasible prepressing method in spacer-filled channels was applied to improve the membrane performance for commercial TFC-FO membranes. Deformation-induced water flux increase rate reached up to 65.41%, meanwhile reverse solute flux had just increased by 24.90%. Such results showed that the membrane performance was effectively improved without complex chemical modification. Stability experiments also demonstrated that the viscous forces in the water permeation process had exerted slight adverse effect on the permeability–selectivity performance of deformed membranes compared to hydraulic pressure. As such, repeated prepressing operation turned out to be effective in terms of stable water flux in long-term filtration process. Therefore, the prepressing operation in spacer-filled channels can be an alternative method to enhance the initial membrane performance and, more significantly, improve the process efficiency in FO. [ABSTRACT FROM AUTHOR]

In this paper, we present the fabrication and characterization of molybdenum microheaters for high-temperature gas sensing applications. The surface morphology of dc magnetron sputtered molybdenum thin films was characterized by scanning electron microscopy and atomic force microscopy. The suspended membrane microheater consumed 104 mW to reach a maximum temperature of 800 °C and showed an absolute thermal resistance of 7.2 °C/mW. Thermal distribution patterns over the active heating area were recorded using FLIR camera. It showed a temperature gradient of 1.18 % from the center of the microheater to its periphery. The thermal and mechanical stabilities of the microheater were analyzed, and its membrane failure at higher operating temperatures was prevented. The microheater membrane deformation at different temperatures was characterized using optical profilometer, and its maximum value was found to be 16.25~\mu \textm at 800 °C. The microheater response to a pulse, continuous pulse train, and constant dc voltages was characterized. Its response and recovery times are in the order of 19 and 34 ms, respectively. It showed a stable temperature with a negligible resistance drift (0.96%) over a period of 600 h. The TiO2 thin film integrated molybdenum microhotplate-based MEMS gas sensor response for CO (5000 ppb) was measured at different operating temperatures (300 °C–700 °C). [ABSTRACT FROM PUBLISHER]

The post-synaptic spines of neuronal dendrites are highly elaborate membrane protrusions. Their anatomy, stability and density are intimately linked to cognitive performance. The morphological transitions of spines are powered by coordinated polymerization of actin filaments against the plasma membrane, but how the membrane-associated polymerization is spatially and temporally regulated has remained ill defined. Here, we discuss our recent findings showing that dendritic spines can be initiated by direct membrane bending by the I-BAR protein MIM/Mtss1. This lipid phosphatidylinositol (PI(4,5)P2) signaling-activated membrane bending coordinated spatial actin assembly and promoted spine formation. From recent advances, we formulate a general model to discuss how spatially concentrated protein-lipid microdomains formed by multivalent interactions between lipids and actin/membrane regulatory proteins might launch cell protrusions.