Bilayer Membranes Research Articles

Phospholipid-functionalized gold electrode for cellular membrane interface studies - interactions between DMPC bilayer and human cystatin C

This work describes the electrochemical studies on the interactions between V57G mutant of human cystatin C (hCC V57G) and membrane bilayer immobilized on the surface of a gold electrode. The electrode was modified with 6-mercaptohexan-1-ol (MCH) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). DMPC was used as a membrane mimetic for monitoring electrochemical changes resulting from the interactions between the functionalized electrode surface and human cystatin C. The interactions between the modified electrode and hCC V57G were investigated by cyclic voltammetry and electrochemical impedance spectroscopy in a phosphate buffered saline (PBS) containing Fe(CN)63−/4- as a redox probe. The electrochemical measurements confirm that fabricated electrode is sensitive to hCC V57G at the concentration of 1 × 10−14 M. The incubation studies carried out at higher concentrations resulted in insignificant changes observed in cyclic voltammetry and electrochemical impedance spectroscopy measurements. The calculated values of surface coverage θR confirm that the electrode is equally covered at higher concentrations of hCC V57G. Measurements of wettability and surface free energy made it possible to determine the influence of individual structural elements of the modified gold electrode on its properties, and thus allowed to understand the nature of the interactions. Contact angle values confirmed the results obtained during electrochemical measurements, indicating the sensitivity of the electrode towards hCC V57G at the concentration of 1 × 10−14 M. In addition, the XPS spectra confirmed the successful anchoring of hCC V57G to the DMPC-functionalized surface.

The Effect of Parent Cell Type on Small Extracellular Vesicle-Derived Vehicle Functionality.

Cell therapies involving c-kit+ progenitor cells (CPCs) and mesenchymal stem cells (MSCs) have been actively studied for cardiac repair. The benefits of such therapies have more recently been attributed to the release of small extracellular vesicles (sEVs) from the parent cells. These sEVs are 30-180nm vesicles containing protein/nucleic acid cargo encapsulated within an amphiphilic bilayer membrane. Despite their pro-reparative effects, sEV composition and cargo loading is highly variable, making it challenging to develop robust therapies with sEVs. Synthetic alternatives have been developed to allow cargo modulation, including prior work from the laboratory, to design sEV-like vehicles (ELVs). ELVs are synthesized from the sEV membrane but allow controlled cargo loading. It is previously shown that loading pro-angiogenic miR-126 into CPC-derived ELVs significantly increases endothelial cell angiogenesis compared to CPC-sEVs alone. Here, they expand on this work to design MSC-derived ELVs and study the role of the parent cell type on ELV composition and function. It is found that ELV origin does affect the ELV potency and that ELV membrane composition can affect outcomes. This study showcases the versatility of ELVs to be synthesized from different parent cells and highlights the importance of selecting ELV source cells based on the desired functional outcomes.

Astragaloside IV-induced BMSC exosomes promote neovascularization and protect cardiac function in myocardial infarction mice via the miR-411/HIF-1α axis

This study focused on investigating the mechanism of the astragaloside IV-induced bone marrow mesenchymal stem cell exosome (AS-IV-MSC-exo)/microRNA(miR)-411/HIF-1α axis in affecting vascular neovascularization and protecting cardiac function in myocardial infarction (MI) mice. Exosomes (MSC-exo and AS-IV-MSC-exo) were separated by differential centrifugation and then characterized. MI mouse models were established by left anterior descending coronary artery ligation. Echocardiography was used to evaluate cardiac function. HE staining and Masson staining were performed to observe myocardial histopathology. Capillary density in the myocardium via immunohistochemistry and quantified the expression of vascular endothelial growth factor (VEGF) via RT-qPCR. The expression of miR-411 and HIF-1α was tested by RT-qPCR and western blot and the targeting relationship of miR-411 and HIF-1α was verified by bioinformatics website and dual luciferase reporter gene assay. Exosomes with lipid bi-layer membrane structure, expressing exosomal surface marker proteins, and being taken up by cardiomyocytes could be successfully isolated utilizing ultracentrifugation. Intramyocardial injection of MSC-exo could restore cardiac function, decrease myocardial pathological changes and collagen deposition, and promote neovascularization in MI mice; the effect of AS-IV-MSC-exo was more significant. The ability of AS-IV-MSC-exo to restore cardiac function, lower myocardial pathological changes and collagen deposition, and promote neovascularization in MI mice was diminished when miR-411 expression in AS-IV-MSC-exo was reduced. Mechanistically, miR-411 was found to target and inhibit HIF-1α expression. Overexpression of HIF-1α impaired the impact of AS-IV-MSC-exo on improving cardiac function and promoting neovascularization in MI mice. AS-IV-MSC-exo improves cardiac function and promoted neovascularization via the miR-411/HIF-1α axis, thereby ameliorating MI.

Si-Drive European Project: Developing Crosslinked Polymer and Composite Membrane Electrolytes for Lithium-Based Batteries

Currently the main application of lithium ion batteries is in portable electronics, but new emerging applications such as electric cars require lower cost, improved cycle life, sustainability, safety and energy density.The ambition of Si-DRIVE European project is proposing next-generation batteries for electric cars built in Europe, designed to ensure recycling above 50%. Si-Drive battery will contain a Silicon anode, which has a high specific capacity, and a high voltage cathode without cobalt to reduce the cost and improve sustainability.As an alternative to conventional organic solvents, ionic liquids have been widely investigated over the years, due to their excellent properties in terms of safety and stability.The 1st generation of electrolytes for Si-Drive includes selected ionic liquids with high ionic conductivity and wide electrochemical stability. The 2nd generation of electrolytes combines the ionic liquids and the precursors of the polymer matrix in the formulation, in order to obtain crosslinked self-standing flexible films. The addition of ceramic super lithium ion conductors to obtain composite polymer electrolytes is also envisaged to improve the electrochemical stability window of the electrolyte.Here we present several different polymer electrolytes and semi interpenetrating polymer networks encompassing ionic liquids and ceramic materials having ionic conductivity > 10 mS/cm at 20 °C, which can be in situ-deposited and crosslinked on top of the electrodes, and combined to form bi-layered electrolyte membranes to tune the compatibility with the electrode materials. The cycling performance with different positive and negative electrodes at ambient temperature is also demonstrated. Acknowledgements: The Si-DRIVE project has received funding from the European Union’s Horizon 2020 Research&Innovation programme, under Grant Agreement 814464. References J.-Y. Hwang, S.-T. Myung, Y.-K. Sun, Chem. Soc. Rev. 46, 3529-3614 (2017)M. Falco, C. Simari, C. Ferrara, J.R. Nair, G. Meligrana, F. Bella, I. Nicotera, P. Mustarelli, M. Winter, C. Gerbaldi, Langmuir 35, 8210-8219 (2019)M. Falco, L. Castro, J.R. Nair, F. Bella, F. Bardé, G. Meligrana, C. Gerbaldi, ACS Appl. Energy Mater. 2, 1600-1607 (2019)M. Falco et al., Electrochem. Commun. 118 106807 (2020)S. Saffirio, M. Falco, G.B. Appetecchi, F. Smeacetto, C. Gerbaldi, Journal of the European Ceramic Society, 42(3), 1023-1032 (2022).

Real-Time Monitoring of Mitochondrial Damage Using Conjugated Oligoelectrolytes.

Conjugated oligoelectrolytes (COEs) comprise a class of fluorescent reporters with tunable optical properties and lipid bilayer affinity. These molecules have proven effective in a range of bioimaging applications; however, their use in characterizing specific subcellular structures remains restricted. Such capabilities would broaden COE applications to understand cellular dysfunction, cell communication, and the targets of different pharmaceutical agents. Here, we disclose a novel COE derivative, COE-CN, which enables the visualization of mitochondria, including morphological changes and lysosomal fusion upon treatment with depolarizing agents. COE-CN is characterized by the presence of imidazolium solubilizing groups and an optically active cyanovinyl-linked distyrylbenzene core with intramolecular charge-transfer characteristics. Our current understanding is that the relatively shorter molecular length of COE-CN leads to weaker binding within lipid bilayer membranes, which allows sampling of internal cellular structures and ultimately to different localization relative to elongated COEs. As a means of practical demonstration, COE-CN can be used to diagnose cells with damaged mitochondria via flow cytometry. Coupled with an elongated COE that does not translocate upon depolarization, changes in ratiometric fluorescence intensity can be used to monitor mitochondrial membrane potential disruption, demonstrating the potential for use in diagnostic assays.

Single-Impact Electrochemistry of Redox Liposomes for the Detection of Virulence Factors

Early detection of pathogens is a key factor for the successful therapy of infectious diseases. Some of the pathogenic bacteria involved in diseases interact with the host by producing compounds that are toxic or disruptive to the cells. As these virulence factors can be easier to spot than the pathogen, strategies of detection can be focused on these released compounds to identify the pathogenic bacterium.[1] Liposomes are vesicles composed of a lipid bilayer membrane, and as such are often used to mimic living cells. Here, the strategy consists in making redox liposomes by encapsulating an electroactive probe in their inner cavity, which will be detected at the electrode.[2] Virulence factors interacting with the vesicles increase the permeability of the lipid membrane and the contents of the liposomes are released over time. This redox probe is then detected with an electrode polarized at the appropriate potential. This work aims to study the single-impact electrochemistry of redox liposomes in different conditions. Previous results indicate that the addition of a surfactant to a liposomal suspension leads to their rupture when they stochastically collide with an ultramicroelectrode.[3] Similarly, virulence factors increase their release or electrolysis of contents upon impact with an ultramicroelectrode.[4] Chronoamperometry measurements recorded at the ultramicroelectrode polarized at the redox potential of the electrochemical probe show impact events (vesicle blocking) and opening events (vesicle reactor) when the encapsulated redox probe is released by the liposome, which are traced back to the presence of pathogenic bacteria.

Polyacrylonitrile (PAN)/carbon nanotube (CNT) electrospun nanofibers: synthesis, characterization, their biocompatibility for L929 fibroblast cells and molecular docking studies

There has been an important interest in to use of electrospun nanomaterials for tissue engineering applications due to the excellent scaffold-cell interaction provided by high interconnectivity and high porosity by electrospun nanofibers. In this study, Polyacrylonitrile (PAN) and carbon nanotube-inserted PAN (PAN/CNT) nanofibers were produced by the electrospinning method and characterized by SEM, FT-IR, and EIS spectroscopy. Both PAN and PAN/CNT nanofibers were obtained beadless and ordered with the average fiber diameters of 277.61 ± 43.6 and 171.01 ± 48.4, respectively. The influence of CNT addition on PAN nanofibers was observed with the decrease of diameter and increase of electrical conductivity of nanofibers. Then, the biocompatibility of PAN and PAN/CNT nanofibers was evaluated by the MTT and AO/EB double-staining experiments. It was observed that the nanofibers showed no cytotoxic effect on L929 fibroblast cells. In the docking experiments, while both PAN and PAN/CNT showed energetically favorable interactions (ΔG = −4.60 kcal/mol; −7.26 kcal/mol, respectively) with the membrane bilayer complex, PAN/CNT formed a more stable binding with the cellular membrane compared to PAN alone. Docking results mechanistically support the more effective increase in the proliferation of L929 fibroblasts at high concentrations in vitro, as PAN/CNT exhibits stronger binding affinity and interaction with the cellular membrane. The increase in electrical conductivity of nanofibers influenced the proliferation positively, as well.

Biomimetic remote handling and sensing devices of multiwalled carbon nanotubes and vanadium pentoxide

Systems capable of managing toxic, reactive and explosive substances through remote handles like light and electricity have enormous technological significance. Here, we report the development of bilayer actuators of multiwalled carbon nanotubes (CNT)/oxidized multiwalled carbon nanotubes (o-CNT) and exfoliated two-dimensional (2D) flakes of vanadium pentoxide (VO) that can precisely handle reactive substances. The unequal photothermal activity of the carbon nanotubes-reconstructed VO were exploited to fabricate the bilayer membranes (CNT-VO) displaying light-controlled shape morphing characteristics (bending speed up to 45° s−1 with light intensity 15 k lux). Similarly, the unparalleled Joule heating effect of o-CNT and VO membranes (o-CNT-VO) was exploited to create electrical voltage-driven actuation (bending speed up to 64.5 °s−1 with an applied voltage of 12 V) of the bilayer membrane. While the light-responsive behaviour of the CNT-VO bilayer membrane was exploited to pick up and drop off reactive chemicals like potassium permanganate (KMnO4), and sodium (Na) metal (up to ten times its body weight), the voltage responsiveness and rose petal effect of o-CNT-VO were used for transporting microdroplets (25 µL) of toxic chemicals like sulfuric acid (H2SO4) and sodium hydroxide (NaOH). Similar to fingers the CNT-VO-based actuators sense the nature of the objects/materials it is picking-up or dropping-off . Owing to the inherent robustness of components, the shape-morphing characteristics of CNT-VO strips survived dipping into acidic, basic and organic liquids.

Interaction of Melatonin with Zwitterionic Model Lipid Membranes

Melatonin is a key hormone secreted by the pineal gland in the brain. It interacts strongly with cell membranes and plays a protective role in several diseases such as Alzheimer's disease, cardiovascular diseases, and cancer. Hence, studies on the interaction of melatonin with lipid bilayer membranes have gained importance. In this regard, the present study aims to analyze the influence of different concentrations (0 to 15 mol%) of melatonin on the thermal and structural properties of zwitterionic stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC) lipid bilayer model systems by using Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). The DSC results have shown that melatonin interacts with the membrane in a concentration-dependent fashion, induces patch formation, and alters the phase behaviour by reducing the main phase transition temperature. FTIR data has shown that increasing the melatonin concentration caused a reduction in the wavenumber of C=O and PO$$_{2}^-$$ antisymmetric stretching vibrations corresponding to the ester carbonyl and phosphate groups of SOPC lipids. This indicates the possibility of strong hydrogen bonding of melatonin with the SOPC lipids and nearby water molecules in the environment, suggesting its preferential location near lipid heads at the interfacial region. These results help to understand the organization and interactions of melatonin with membranes and provide insights to develop safe melatonin-based formulations for pharmaceutical applications.

Dynamic Behavior and Interaction Mechanism of Soil Organic Matter in Water Systems: A Coarse-Grained Molecular Dynamics Study.

Investigating soil organic matter's (SOM) microscale assembly and functionality is challenging due to its complexity. This study constructs comparatively realistic SOM models, including diverse components such as Leonardite humic acid (LHA), lipids, peptides, carbohydrates, and lignin, to unveil their spontaneous self-assembly behavior at the mesoscopic scale through microsecond coarse-grained molecular dynamics simulations. We discovered an ordered SOM aggregation creating a layered phase from its hydrophobic core to the aqueous phase, resulting in an increasing O/C ratio and declining structural amphiphilicity. Notably, the amphiphilic lipids formed a bilayer membrane, partnering with lignin to constitute SOM's hydrophobic core. LHA, despite forming a layer, was embedded within this structure. The formation of such complex architectures was driven by nonbonded interactions between components. Our analysis revealed component-dependent diffusion effects within the SOM system. Lipids, peptides, and lignin showed inhibitory effects on self-diffusion, while carbohydrates facilitated diffusion. This study offers novel insights into the dynamic behavior and assembly of SOM components, introducing an effective approach for studying dynamic SOM mechanisms in aquatic environments.

Generation of electric potential difference by chromatophores from photosynthetic bacteria in the presence of trehalose under continuous illumination

Measurement of the electrical potential difference (Δψ) in membrane vesicles (chromatophores) from the purple bacterium Rhodobacter sphaeroides, associated with the surface of a nitrocellulose membrane filter (MF), impregnated with phospholipid solution in decane, as well as immersed inside it, in the presence of exogenous mediators and disaccharide trehalose, demonstrated an increase in the amplitude and stabilization of the signal under continuous illumination. The ascorbate/N,N,N′N′-tetramethyl-p-phenylenediamine pair and ubiquinone-0 were used as mediators (electron donor and acceptor), respectively. Although the stabilization of photoelectric responses under long-term continuous illumination was observed in both cases of immobilization of chromatophores, only when the samples were immersed inside the MF, the functional activity of the reaction centers was maintained for a month when they were stored in the dark at room temperature. Stable photoresponses are probably associated with the preservation of the integrity of chromatophore proteins inside MF pores. The stabilizing effect of the bioprotector trehalose may be due to both its effect on RC proteins and on the phospholipid bilayer membrane. The results obtained will expand modern ideas about the use of semi-synthetic structures based on various intact photosynthetic systems capable of converting solar energy into an electrochemical form.

Poly(lactic acid/caprolactone) bilayer membrane achieves bone regeneration through a prolonged barrier function.

Guided bone regeneration (GBR) is a treatment strategy used to recover bone volume. Barrier membranes are a key component of GBR protocols, and their properties can impact treatment outcomes. This study investigated the efficacy of an experimental, slow-degrading, bilayer barrier membrane for application in GBR using in vivo animal models. A synthetic copolymer of poly(lactic acid/caprolactone) (PLCL) was used to prepare a slow-degrading bilayer membrane. The biodegradability of PLCL was evaluated by subcutaneous implantation in a rat model. The barrier function of the PLCL membrane was investigated in a rat calvaria defect model and compared with commercially available membranes composed of type I collagen (Col) and poly(lactic-co-glycolic acid) (PLGA). An alveolar bone defect model in beagle dogs was used to simulate GBR protocols to evaluate the bone regeneration ability of the experimental PLCL membrane. The PLCL membrane showed slow biodegradation, resulting in an efficient and prolonged barrier function compared with commercial materials. In turn, this barrier function enabled the space-making ability of PLCL membrane and facilitated bone regeneration. In the alveolar bone defect model, significantly greater regeneration was achieved by treatment with PLCL membrane compared with Col and PLGA membranes. Additionally, a continuous alveolar ridge contour was observed in PLCL-treated bone defects. In conclusion, the PLCL bilayer membrane is a promising biomaterial for use in GBR given its slow degradation and prolonged barrier function.

19F-NMR studies of the impact of different detergents and nanodiscs on the A2A adenosine receptor.

For the A2A adenosine receptor (A2AAR), a class A G-protein-coupled receptor (GPCR), reconstituted in n-dodecyl-β-D-maltoside (DDM)/‌‌‌‌‌cholesteryl hemisuccinate (CHS) mixed micelles, previous 19F-NMR studies revealed the presence of multiple simultaneously populated conformational states. Here, we study the influence of a different detergent, lauryl maltose neopentyl glycol (LMNG) in mixed micelles with CHS, and of lipid bilayer nanodiscs on these conformational equilibria. The populations of locally different substates are pronouncedly different in DDM/‌‌‌‌‌CHS and LMNG/‌‌‌‌‌CHS micelles, whereas the A2AAR conformational manifold in LMNG/‌‌‌‌‌CHS micelles is closely similar to that in the lipid bilayer nanodiscs. Considering that nanodiscs represent a closer match of the natural lipid bilayer membrane, these observations support that LMNG/‌‌‌‌‌CHS micelles are a good choice for reconstitution trials of class A GPCRs for NMR studies in solution.

Molecular Machines For The Control Of Transmembrane Transport.

Nature embeds some of its molecular machinery, including ion pumps, within lipid bilayer membranes. This has inspired chemists to attempt to develop synthetic analogues to exploit membrane confinement and transmembrane potential gradients, much like their biological cousins. In this perspective, we outline the various strategies by which molecular machines─molecular systems in which a nanomechanical motion is exploited for function─have been designed to be incorporated within lipid membranes and utilized to mediate transmembrane ion transport. We survey molecular machines spanning both switches and motors, those that act as mobile carriers or that are anchored within the membrane, mechanically interlocked molecules, and examples that are activated in response to external stimuli.

Niosomal-Based Drug Delivery Platforms: A Promising Therapeutic Approach to Fight Staphylococcus aureus Drug Resistance

Staphylococcus aureus, a prominent bacterial pathogen, presents formidable medical challenges owing to its rapid development of resistance. The emergence of multidrug resistant (MDR) S. aureus strains has become a pressing concern for healthcare systems, driving researchers to explore novel therapeutic strategies for managing infections associated with this pathogen. In this pursuit, niosomal-based platforms have emerged as promising candidates to effectively target S. aureus and fight conventional antimicrobial resistance. Niosomes comprise a bilayer membrane formed by nonionic surfactants, which can encapsulate both hydrophilic and hydrophobic drugs. These nanoparticles are known as vesicular delivery systems and have many advantages, such as low cost, less toxicity, and more flexibility and stability. Moreover, niosomes, being an effective drug delivery system, can directly interact with the bacterial cell envelope, thereby enhancing the pharmacokinetic activities of drugs at infected sites. A niosome-based delivery system can effectively treat S. aureus infections by destroying the biofilm community, increasing intracellular targeting, and enhancing the antibacterial activity. The main mechanisms of action of niosomes against resistant S. aureus strains involve the ability to resist enzymatic degradation, controlled release profile, and targeted drug delivery, which can provide an effective dosage of antimicrobial agents at the site of actions. In addition, niosomes have the potential to transfer wide-spectrum materials from different classes of antibiotics to nonantibiotic antimicrobial agents, such as natural compounds, antimicrobial peptides, and metallic nanoparticles. The combination of polymeric materials in the structure of a niosomal formulation could improve their bioavailability, loading capacity, and therapeutic efficacy for different applications. Furthermore, niosomes could find application in photodynamic therapy, offering a promising alternative to conventional treatments for eradicating drug-resistant S. aureus isolates. Finally, niosomal nanocarriers can be developed for delivering the drugs to desired sites by different routes of administration and could be considered a powerful strategy for overcoming the therapeutic obstacles caused by MDR S. aureus.

Curvature-enhanced membrane asymmetry slows down protein diffusion

Diffusion of transmembrane proteins plays a vital role in various cellular processes, such as endocytosis, raft formation and signal transduction. Current understanding of protein diffusion dynamics in lipid membranes is mostly based on hydrodynamic analyses, in which lipid membrane is simply treated as a thin layer of viscous liquid, same for highly curved ones. Therefore, how the mechanical state of highly curved membranes may affect the transmembrane protein diffusion remains unclear. In this study, we employed molecular dynamics (MD) simulations to analyse membrane curvature effect on the diffusion of cylindrically shaped Aquaporin-0 (AQP0) protein. Slowing down of protein diffusion with the increase in membrane curvature was observed. The possible contributions from membrane tension and asymmetric pressure profile were systematically investigated by simulating the protein diffusion dynamics in planar membranes with various tension levels or with various lipid number ratios between the two leaflets, respectively. We found no significant effect of membrane tension on AQP0 diffusion. Instead, the asymmetric pressure profile present in highly curved bilayer membranes was identified as a key factor that contributes to the slowing down of transmembrane protein diffusion. Our work thus contributes to a more complete picture of transmembrane protein diffusion on highly curved biological membranes.

Understanding the electrochemical interaction between the hybrid bilayer lipid membranes and amyloid‐β

AbstractBackgroundBiomimetic membrane systems can be deposited onto conductive metal surfaces to study the physical properties of membranes as well as the behaviour of proteins within these membranes using electrochemical and surface analytical techniques [1]. Although there are several types of biomimetic membrane, hybrid bilayer lipid membranes (HBLMs) have attracted wide interest. Traditionally, HBLMs have been developed by electrodepositing alkanethiol self‐assembled monolayers onto gold surfaces, which can then be further modified by depositing a secondary phospholipid layer to form the HBLM. Although HBLMs have been widely regarded due to them being robust, relatively straightforward to make, as well as being easy to modify according to the users needs, several concerns surround HBLMs including their reduced fluidity compared to true cell membranes. This is due to the alkanethiol layer being crystalline in nature and more densely packed, resulting in difficulty to reconstitute transmembrane proteins within them.MethodScreen‐printed carbon electrodes are modified with diazonium based phenyl alkyl groups using different protocols to evaluate the biomimetic differences of these novel HBLMs. 2,2‐diphenyl‐1‐picrylhydrazyl is used to prevent the formation of polyaryl layers on the surface of the electrode, hence limiting the electrodeposition to a monolayer. The HBLMs are formed by depositing the second layer in the form of dihexadecyl phosphate, which are analyzed using differential pulse voltammetry, ellipsometry, and X‐ray photoelectron spectroscopy.ResultThe different HBLMs presented are embedded with amyloid‐β1‐42 (Aβ42), the hallmark protein implicated in Alzheimer’s Disease, to assess the protein‐membrane interactions using HBLMs. Aβ42 is known to aggregate to form dimers, oligomers, fibrils, and plaques. Hence using electrochemical techniques, we are able to monitor the aggregation of Aβ42 in the HBLMs. The aggregation process was accelerated by the presence of the bilayer membrane.ConclusionThe electrochemical platform presented here enables us to understand how the interaction of amyloid‐β with the bilayer membrane can alter the aggregation pathways and also affect the formation of toxic oligomer species.

Alteration of Average Thickness of Lipid Bilayer by Membrane-Deforming Inclusions.

Thickness of lipid bilayer membranes is a key physical parameter determining membrane permeability and stability with respect to formation of through pores. Most membrane inclusions or impurities like amphipathic peptides, transmembrane peptides, lipid inclusions of a different molecular shape, lipid domains, and protein-lipid domains, locally deform the membrane. The detailed structure of the locally deformed region of the membrane is a kind of "fingerprint" for the inclusion type. However, most experimental methods allow determining only averaged parameters of membranes with incorporated inclusions, thus preventing the direct obtaining of the characteristics of the inclusion. Here we developed a model that allows the obtaining of characteristic parameters of three types of membrane inclusions (amphipathic peptides, transmembrane peptides, monolayer lipid patches) from experimentally observable dependencies of the average thickness of lipid bilayer on the surface concentration of the inclusions. In the case of amphipathic peptides, the model provided the peptide parameters that were in qualitative agreement with the available experimental data.

Exosomal miRNAs as Biomarkers of Ischemic Stroke.

Exosomes are small lipid bilayer membrane particles released from all living cells into the extracellular environment. They carry several molecules and have a critical role in cell-cell communication under physiological and pathological conditions. In recent decades, exosomes, and especially their cargo, have emerged as a promising tool for several clinical conditions. However, the literature has become increasingly unambiguous in defining the role of exosomes in chronic cerebrovascular diseases. Because they can pass through the blood-brain barrier, they have great potential to reflect intracerebral changes. They can, thus, provide valuable insight into the mechanisms of central nervous system diseases. The purpose of this review is to describe the literature on the role of exosomal miRNA, which represents the most widely investigated exosomal biomarker, in strokes. First, we provide an overview of exosomes, from biology to isolation and characterization. Then, we describe the relationship between exosomes and stroke pathogenesis. Finally, we summarize the human studies evaluating exosomal miRNA biomarkers of stroke. Although the collective literature supports the potential use of exosomal miRNA as biomarkers of ischemic stroke, there are still several limitations hampering their introduction into clinical practice.

Repurposing phenothiazines for cancer therapy: compromising membrane integrity in cancer cells

The limitations of current cancer therapies, including the increasing prevalence of multidrug resistance, underscore the urgency for more effective treatments. One promising avenue lies in the repurposing of existing drugs. This review explores the impact of phenothiazines, primarily used as antipsychotic agents, on key mechanisms driving tumor growth and metastasis. The cationic and amphiphilic nature of phenothiazines allows interaction with the lipid bilayer of cellular membranes, resulting in alterations in lipid composition, modulation of calcium channels, fluidity, thinning, and integrity of the plasma membrane. This is especially significant in the setting of increased metabolic activity, a higher proliferative rate, and the invasiveness of cancer cells, which often rely on plasma membrane repair. Therefore, properties of phenothiazines such as compromising plasma membrane integrity and repair, disturbing calcium regulation, inducing cytosolic K-RAS accumulation, and sphingomyelin accumulation in the plasma membrane might counteract multidrug resistance by sensitizing cancer cells to membrane damage and chemotherapy. This review outlines a comprehensive overview of the mechanisms driving the anticancer activities of phenothiazines derivates such as trifluoperazine, prochlorperazine, chlorpromazine, promethazine, thioridazine, and fluphenazine. The repurposing potential of phenothiazines paves the way for novel approaches to improve future cancer treatment.