Changes In Membrane Structure Research Articles

Polysaccharide-Based Coacervate Microgel Bearing Cationic Peptides That Achieve Dynamic Cell-Membrane Structure Alteration and Facile Cytosolic Infusion of IgGs.

Conjugates of the biocompatible polysaccharide pullulan with a cell membrane permeabilizing peptide L17E (PL-L17Es) were prepared with the aim of producing complex coacervates with pronounced intracellular antibody (IgG) delivery activity and stable structures. Coacervates with diameters of a few μm were formed simply by mixing PL-L17Es with IgG labeled with negatively charged fluorescent moieties of Alexa Fluor 488 [IgG(AF488)]. The coacervate resulted in a pronounced cytosolic infusion of IgG(AF488) and IgG binding to the target proteins inside the cell. The droplet structures were maintained even under high salt conditions, and the fluorescence in the droplet was not recovered after photobleaching, suggesting the formation of complex coacervate microgels. Dynamic changes in cell membrane structure to entrap the coacervate microgels were captured by confocal and electron microscopy, resulting in cytosolic IgG infusion. The use of M-lycotoxin instead of L17E resulted in a coacervate microgel with marked IgG delivery activity even in the presence of serum. Successful IgG delivery to primary hepatocytes, undifferentiated induced pluripotent stem (iPS) cells, and iPS cell-derived intestinal epithelial cells was also achieved. The construction of complex coacervate microgels with design flexibility and the validity of intracellular IgG delivery with high salt stability were thus demonstrated.

Repurposing flubendazole for glioblastoma ferroptosis by affecting xCT and TFRC proteins.

New uses of old drugs hold great promise for clinical translation. Flubendazole, an FDA-approved antiparasitic drug, has been shown to target p53 and promote apoptosis in glioblastoma (GBM) cells. However, its damaging mechanism in GBM remains elusive. Herein, we explored the ferroptosis-inducing ability of flubendazole on GBM cells. After treating glioma cell lines U251 and LN229 with the flubendazole (DMSO <1‰), cell viability was inhibited in a concentration-dependent manner (IC50 for LN229 = 0.5331 μM, IC50 for U251 = 0.6809 μM), attributed to the induction of ferroptosis, as evidenced by increased MDA levels, accumulation of ROS and lipid peroxides, change in mitochondrial membrane potential and structure. Protein analysis related to ferroptosis showed upregulation of TFRC, DMT1 and p53, alongside downregulation of xCT, FHC and GPX4 (p < 0.05). All-atom docking studies demonstrated that flubendazole bound closely with xCT, and TFRC, validating its role in inducing glioma ferroptosis via modulation of these proteins. Notably, flubendazole could damage the glioblastoma stem cells (GSC) that are typically resistant to other therapies, thereby possessing advantages in stopping glioma recurrence. This study delved into the mechanisms of flubendazole-induced ferroptosis in glioma, broadening its application and providing new ideas for new uses of other old drugs.

TMEM63B scrambles phospholipids in response to changes in membrane structure.

TMEM63B scrambles phospholipids in response to changes in membrane structure.

Infrared spectral profiling of demyelinating activity in multiple sclerosis brain tissue

Multiple sclerosis (MS) is a leading cause of non-traumatic disability in young adults. The highly dynamic nature of MS lesions has made them difficult to study using traditional histopathology due to the specificity of current stains. This requires numerous stains to track and study demyelinating activity in MS. Thus, we utilized Fourier transform infrared (FTIR) spectroscopy to generate holistic biomolecular profiles of demyelinating activities in MS brain tissue. Multivariate analysis can differentiate MS tissue from controls. Analysis of the absorbance spectra shows profound reductions of lipids, proteins, and phosphate in white matter lesions. Changes in unsaturated lipids and lipid chain length indicate oxidative damage in MS brain tissue. Altered lipid and protein structures suggest changes in MS membrane structure and organization. Unique carbohydrate signatures are seen in MS tissue compared to controls, indicating altered metabolic activities. Cortical lesions had increased olefinic lipid content and abnormal membrane structure in normal appearing MS cortex compared to controls. Our results suggest that FTIR spectroscopy can further our understanding of lesion evolution and disease mechanisms in MS paving the way towards improved diagnosis, prognosis, and development of novel therapeutics.

Oxidation of lipid membrane cholesterol by cholesterol oxidase and its effects on raft model membrane structure

The effects of a peripheral protein – cholesterol oxidase (3β-hydroxysteroid oxidase, ChOx) on the characteristics of model lipid membranes composed of cholesterol, cholesterol:sphingomyelin (1:1), and the raft model composed of DOPC:Chol:SM (1:1:1) were investigated using two membrane model systems: the flat monolayer prepared by the Langmuir technique and the curved model consisting of liposome of the same lipids. The planar monolayers and liposomes were employed to follow membrane cholesterol oxidation to cholestenone catalyzed by ChOx and changes in the lipid membrane structure accompanying this reaction. Changes in the structure of liposomes in the presence of the enzyme were reflected in the changes of hydrodynamic diameter and fluorescence microscopy images, while changes of surface properties of planar membranes were evaluated by grazing incidence X-ray diffraction (GIXD) and Brewster angle microscopy. UV-Vis absorbance measurements confirmed the activity of the enzyme in the tested systems. A better understanding of the interactions between the enzyme and the cell membrane may help in finding alternative ways to decrease excessive cholesterol levels than the common approach of treating hypercholesterolemia with statins, which are not free from undesirable side effects, repeatedly reported in the literature and observed by the patients.

Antibacterial activity and biosynthetic potential of Streptomyces sp. PBR19, isolated from forest rhizosphere soil of Assam.

An Actinomycetia isolate, designated as PBR19, was derived from the rhizosphere soil of Pobitora Wildlife Sanctuary (PWS), Assam, India. The isolate, identified as Streptomyces sp., shares a sequence similarity of 93.96% with its nearest type strain, Streptomyces atrovirens. This finding indicates the potential classification of PBR19 as a new taxon within the Actinomycetota phylum. PBR19 displayed notable antibacterial action against some ESKAPE pathogens. The ethyl acetate extract of PBR19 (EtAc-PBR19) showed the lowest minimum inhibitory concentration (MIC) of ≥ 0.195µg/mL against Acinetobacter baumannii ATCC BAA-1705. A lower MIC indicates higher potency against the tested pathogen. Scanning electron microscope (SEM) findings revealed significant changes in the cytoplasmic membrane structure of the pathogen. This suggests that the antibacterial activity may be linked to the disruption of the microbial membrane. The predominant chemical compound detected in the EtAc-PBR19 was identified as phenol, 3,5-bis(1,1-dimethylethyl), comprising 48.59% of the area percentage. Additionally, PBR19 was found to contain the type II polyketide synthases (PKS type II) gene associated with antibiotic synthesis. The predicted gene product of PKSII was identified as the macrolide antibiotic Megalomicin A. The taxonomic distinctiveness, potent antibacterial effects, and the presence of a gene associated with antibiotic synthesis suggest that PBR19 could be a valuable candidate for further exploration in drug development and synthetic biology. The study contributes to the broader understanding of microbial diversity and the potential for discovering bioactive compounds in less-explored environments.

Investigation of diabetes-related molecular changes in embryo-endometrium crosstalk

The primary aim of this study was to explore the impact of diabetes on matrix metalloproteases and tissue inhibitors, crucial factors for successful implantation, and to elucidate the molecular mechanisms that undergo changes in the endometrium and the embryo during diabetic pregnancies. In this investigation, we established a streptozotocin-induced diabetic pregnant rat model. Microarray analysis followed by RT-PCR was utilized to identify gene regions exhibiting expression alterations. Subsequently, we assessed the effects of MMPs and tissue inhibitors using ELISA and immunohistochemistry techniques, in addition to analyzing changes at the genetic level. Diabetes led to the upregulation of MMP3, MMP9, and MMP20 on the 6.5th day of pregnancy, while causing the downregulation of MMP3, MMP9, and MMP11 on the 8.5th day of pregnancy. TIMP1 expression was downregulated on the 8.5th day compared to the control group. No statistically significant differences were observed between the groups regarding other TIMP expressions. KEGG pathway analysis revealed that diabetes induced alterations in the expression of genes associated with certain microRNAs, as well as signaling pathways such as cAMP, calcium, BMP, p53, MAPK, PI3K-Akt, Jak-STAT, Hippo, Wnt, and TNF. Additionally, gene ontology analysis unveiled changes in membrane structures, extracellular matrix, signaling pathways, ion binding, protein binding, cell adhesion molecule binding, and receptor-ligand activity. This study serves as a valuable guide for investigating the mechanisms responsible for complications in diabetic pregnancies. By revealing the early-stage effects of diabetes, it offers insight into the development of new diagnostic and treatment approaches, ultimately contributing to improved patient care.

Pervaporation Membranes Based on Polyelectrolyte Complex of Sodium Alginate/Polyethyleneimine Modified with Graphene Oxide for Ethanol Dehydration.

Pervaporation is considered the most promising technology for dehydration of bioalcohols, attracting increasing attention as a renewable energy source. In this regard, the development of stable and effective membranes is required. In this study, highly efficient membranes for the enhanced pervaporation dehydration of ethanol were developed by modification of sodium alginate (SA) with a polyethylenimine (PEI) forming polyelectrolyte complex (PEC) and graphene oxide (GO). The effect of modifications with GO or/and PEI on the structure, physicochemical, and transport characteristics of dense membranes was studied. The formation of a PEC by ionic cross-linking and its interaction with GO led to changes in membrane structure, confirmed by spectroscopic and microscopic methods. The physicochemical properties of membranes were investigated by a thermogravimetric analysis, a differential scanning calorimetry, and measurements of contact angles. The theoretical consideration using computational methods showed favorable hydrogen bonding interactions between GO, PEI, and water, which caused improved membrane performance. To increase permeability, supported membranes without treatment and cross-linked were developed by the deposition of a thin dense layer from the optimal PEC/GO (2.5%) composite onto a developed porous substrate from polyacrylonitrile. The cross-linked supported membrane demonstrated more than two times increased permeation flux, higher selectivity (above 99.7 wt.% water in the permeate) and stability for separating diluted mixtures compared to the dense pristine SA membrane.

Protopanaxadiol Targeting Membrane Induces HepG2 Cell Apoptosis Via Raft-like Formation and Tubulation Disruption.

Protopanaxadiol (PPD), which has a molecular structure similar to cholesterol, is a potent anticancer agent that has been proposed to target the lipid membrane for the pharmacological effects. However, the underlying mechanism by which PPD modulates the cell membrane leading to cancer cell death is not be fully understood. In this work, we used single cell infrared spectroscopy, scanning electron microscopy and confocal microscopy to investigate the effects of PPD on human hepatocellular carcinoma (HepG2) cells, focusing on the change in membrane structure. We found that PPD significantly reduced the number of membrane tubules over the course of treatment. Interestingly, the addition of PPD could promote the formation of lipid raft-like domains (PPD rafts) and even restore the domain disruption caused by methyl-beta-cyclodextrin depletion of membrane cholesterol. In addition, PPD pre-treatment may increase the induction effect of FasL, which impairs cell viability, although it does not appear to be beneficial for Fas clustering in the PPD rafts. Collectively, these results highlight a non-classical mechanism by which PPD induces HepG2 apoptosis by directly affecting the physical properties of the cell membrane, providing a novel insight into understanding membrane-targeted therapy.

Enhanced Separation Performance of Graphene Oxide Membrane through Modification with Graphitic Carbon Nitride

The treatment of tritiated nuclear wastewater is facing greater challenges with the continuous expansion of the nuclear industry. The key to solving the issue of detritium in low-abundance tritium water lies in developing highly efficient and cost-effective hydrogen isotope separation technology. Graphene oxide (GO) membrane separation method exhibits greater potential compared to other existing energy-intensive technologies for the challenging task of hydrogen isotope separation in nuclear wastewater. In recent years, researchers have explored few strategies to enhance the performance of graphene oxide (GO) membranes in hydrogen isotope water treatment, recognizing the current limitations in separation efficiency. In this study, the GO/g-C3N4 composite membrane has been successfully employed for the first time in the separation of hydrogen isotopes in water. A series of GO membranes were prepared and their performances were tested by a self-made experimental device. As a result, the separation performance of the GO membrane was enhanced by the modification with graphitic carbon nitride (g-C3N4). The permeation rate of the GO/g-C3N4 membrane was higher than that of the GO membrane, while maintaining a high separation factor. Our study also demonstrated that this phenomenon can be attributed to the changes in membrane structure at the microscopic scale. The H/D separation factor and the permeate flux of the composite membrane containing g-C3N4 of 6.7% by mass were 1.10 and 7.2 × 10−5 g·min−1·cm−2 are both higher than that of the GO membrane under the same experimental conditions, which is promising for the isotope treatment.

Modulation of Phospholipase A2 Membrane Activity by Anti-inflammatory Drugs.

The phospholipase A2 (PLA2) superfamily consists of lipolytic enzymes that hydrolyze specific cell membrane phospholipids and have long been considered a central hub of biosynthetic pathways, where their lipid metabolites exert a variety of physiological roles. A misregulated PLA2 activity is associated with mainly inflammatory-derived pathologies and thus has shown relevant therapeutic potential. Many natural and synthetic anti-inflammatory drugs (AIDs) have been proposed as direct modulators of PLA2 activity. However, despite the specific chemical properties that these drugs share in common, little is known about the indirect modulation able to finely tune membrane structural changes at the precise lipid-binding site. Here, we use a novel experimental strategy based on differential scanning calorimetry to systematically study the structural properties of lipid membrane systems during PLA2 cleavage and under the influence of several AIDs. For a better understanding of the AIDs-membrane interaction, we present a comprehensive and comparative set of molecular dynamics (MD) simulations. Our thermodynamic results clearly demonstrate that PLA2 cleavage is hindered by those AIDs that significantly reduce the lipid membrane cooperativity, while the rest of the AIDs oppositely tend to catalyze PLA2 activity to different extents. On the other hand, our MD simulations support experimental results by providing atomistic details on the binding, insertion, and dynamics of each AID on a pure lipid system; the drug efficacy to impact membrane cooperativity is related to the lipid order perturbation. This work suggests a membrane-based mechanism of action for diverse AIDs against PLA2 activity and provides relevant clues that must be considered in its modulation.

Effect of citric acid on cell membrane structure and function of Issatchenkia terricola WJL-G4.

This study aimed to investigate the changes of cell membrane structure and function of Issatchenkia terricola under citric acid by performing physiological analysis. The membrane integrity, surface hydrophobicity, structure, fluidity, apoptosis, and fatty acid methyl esters composition of I. terricola WJL-G4 cells were determined by propidium iodide staining, microbial adhesion to hydrocarbon test, transmission electron microscopy analysis, fluorescence anisotropy, flow cytometry, and gas chromatography-mass, respectively. The results showed that with the increasing of citric acid concentrations, the cell vitality, membrane integrity, and fluidity of I. terricola reduced; meanwhile, apoptosis rate, membrane permeable, hydrophobicity, and ergosterol contents augmented significantly. Compared to control, the activities of Na+, K+-ATPase, and Ca2+, Mg2+-ATPase increased by 3.73-fold and 6.70-fold, respectively, when citric acid concentration increased to 20g l-1. The cells cracked and their cytoplasm effused when the citric acid concentration reached 80g l-1. I. terricola could successfully adjust its membrane structure and function below 60g l-1 of citric acid. However, for citric acid concentrations above 80g l-1, its structure and function were dramatically changed, which might result in reduced functionality.

DP1, a multifaceted synthetic peptide: Mechanism of action, activity and clinical potential

AimsMicrobial infections remain a leading cause of mortality worldwide, with Staphylococcus aureus (S. aureus) being a prominent etiological agent, responsible for causing persistent bacterial infections in humans. It is a nosocomial, opportunistic pathogen, capable to propagate within the bloodstream and withstand therapeutic interventions. In the current study, a novel, indigenously designed synthetic antimicrobial peptide (sAMP) has been evaluated for its antimicrobial potential to inhibit the growth and proliferation of S. aureus. Main methodsThe sAMP, designed peptide (DP1) was evaluated for its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against a panel of pathogenic bacterial strains. Membrane mechanistic studies were performed by measuring membrane conductivity via dielectric spectroscopy and visualizing changes in bacterial membrane structure through field emission scanning electron microscopy (FE-SEM). Further, DP1 was tested for its in vivo antimicrobial potential in an S. aureus-induced systemic infection model. Key findingsThe results indicated that DP1 has the potential to inhibit the growth and proliferation of a broad spectrum of Gram-positive, Gram-negative and multidrug-resistant (MDR) bacterial strains. Strong bactericidal effect attributed to change in electrical conductivity of the bacterial cells leading to membrane disruption was observed through dielectric spectroscopy and FE-SEM micrographs. Further, in the in vivo murine systemic infection study, 50 % reduction in S. aureus bioburden was observed within 1 day of the administration of DP1. SignificanceThe results indicate that DP1 is a multifaceted peptide with potent bactericidal, antioxidant and therapeutic properties. It holds significance as a novel drug candidate to effectively combat S. aureus-mediated systemic infections.

Mechanistic insights into microwave-accelerated permeation through graphene-based membranes

Two-dimensional (2D) membranes, composed of stacked 2D nanomaterials, are increasingly utilized in separation fields due to their structured interlayer channels and ease of modification. The application of microwave technology to 2D membrane separation enhances permeability, but the unclear strengthening mechanism limits the further applications of this technique. This study aims to elucidate the fundamental principle behind microwave-accelerated permeability by investigating the performance of two distinct 2D membranes in response to microwaves: a microwave-transparent graphene oxide (GO) membrane and a microwave-absorbing GO-based membrane doped with molybdenum disulfide (MoS2-GO). Experimental results demonstrate that compared to conventional heating, microwave irradiation amplifies water and ethanol permeation flux through the GO membrane by 122% and 154%, respectively, without observed changes in membrane structure via SEM, XRD, and Raman analyses. In addition, the microwave accelerated permeation also occurs (by 110%) when Rhodamine B - aqueous solution was used as feed liquid, while the rejection rate was remained at above 99%, indicating the promising applications of microwave technology in sewage treatment. Further experiments show that the microwave-induced augmentation of water/ethanol permeation through the GO membrane was primarily governed by the dielectric loss values of the feed liquid. In contrast, this dependence vanished in the MoS2-GO membrane, indicating that accelerated permeation was mainly determined by the interaction between microwaves and diffusing molecules in the 2D channels, disrupted by microwave absorbing MoS2 in the latter case. These findings offer comprehensive insights into the enhancement of membrane permeation induced by microwave irradiation.

Dynamic modeling of chemical membrane degradation in polymer electrolyte membrane fuel cells: Effect of precipitated Pt particles

Chemical membrane degradation in polymer electrolyte membrane fuel cells operated under real conditions is often accompanied and affected by Pt catalyst degradation. This study investigates the effects of both artificially impregnated Pt particles and Pt migration on chemical membrane degradation are numerically investigated. For the first time, the impact of Pt migration is numerically analyzed. Membrane structural changes with coupled chemical membrane and Pt degradations are proposed. For Pt particles that are artificially impregnated in the membrane, yielding a Pt content of up to 50 mol% Pt, the membrane degrades at the fastest rate at moderate Pt contents (2 mol% Pt). The impregnated Pt particles promote the conversion of Fe3+ to Fe2+, which adversely impacts the membrane durability. The decrease in Pt content leads to reduction in both the Fe2+ conversion time and trend. In comparison, the naturally precipitated Pt particles in the membrane from the degraded Pt catalysts in the CL, have demonstrated a Pt content consistently lower than 2 mol% Pt. As a result, the chemical degradation rate of real fuel cells accelerates significantly with increasing Pt particle concentration. The chemical degradation rate increases with the gas solubility at the pore/electrolyte interface. With higher gas solubility, the peak location of chemical membrane degradation shifts from the anode side to the cathode side.

The intricate link between membrane lipid structure and composition and membrane structural properties in bacterial membranes.

It is now evident that the cell manipulates lipid composition to regulate different processes such as membrane protein insertion, assembly and function. Moreover, changes in membrane structure and properties, lipid homeostasis during growth and differentiation with associated changes in cell size and shape, and responses to external stress have been related to drug resistance across mammalian species and a range of microorganisms. While it is well known that the biomembrane is a fluid self-assembled nanostructure, the link between the lipid components and the structural properties of the lipid bilayer are not well understood. This perspective aims to address this topic with a view to a more detailed understanding of the factors that regulate bilayer structure and flexibility. We describe a selection of recent studies that address the dynamic nature of bacterial lipid diversity and membrane properties in response to stress conditions. This emerging area has important implications for a broad range of cellular processes and may open new avenues of drug design for selective cell targeting.

Photovoltage transient technique: an alternative approach to real-time analysis of membrane interface dynamic processes

&lt;sec&gt;The dynamic interactions between active molecules and the cell membrane play a crucial role in various fundamental biological processes. The photovoltage transient technique developed in recent years has provided an an &lt;i&gt;in situ&lt;/i&gt;, real-time, and non-invasive approach to studying dynamic processes at the membrane interface. In this technique, the photoelectric response of silicon wafers is used to generate charges and record voltage transient pulses in the charging and discharging process of phospholipid membranes. These pulses directly reflect the instantaneous structure and properties of the membrane. By analyzing the temporal evolution of voltage pulses, the dynamic changes in membrane structure induced by molecular actions can be elucidated. In particular, this technique provides valuable insights into the timing of transitions between different functional states. In this paper, the working principle, equipment setup, and data processing methods used in photovoltage transient analysis are comprehensively reviewed. Furthermore, the use of supported phospholipid bilayers as model cell membranes highlights recent progress of this technique in investigating the mechanisms underlying membrane interactions of active molecules such as surfactants, polymers, peptides, and nanoparticles. Finally, its advantages and limitations are evaluated, and its development prospects are discussed.&lt;/sec&gt;&lt;sec&gt;The photovoltage transient technique is initially used to analyze the charging and discharging curves, as well as the hydration process, of single- and multi-layered membranes composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) phospholipids. Previously, X-ray diffraction (XRD) and quartz crystal microbalance with dissipation (QCM-D) technology were commonly utilized for the real-time monitoring of the swelling process in phospholipid membranes, providing the information about changes in mass and thickness of Z-direction layers. In contrast, the photovoltage transient technique presents additional insights into the kinetics of the swelling process and timing of transitions between different stages. The present study demonstrates the effectiveness of photovoltage transient technique in real-time monitoring of membrane interface processes, specifically, it quantitatively measures the characteristic &lt;i&gt;τ&lt;/i&gt; value of DOPC phospholipid membrane, thereby enabling further development of quantitative analysis method for this technique. Then, the photovoltage transient technique, in conjunction with giant unilamellar vesicle (GUV) leakage assays, atomic force microscopy (AFM) and QCM-D, is employed to monitor the structural perturbation of surfactants (TTAB) and polymers (Brij35 and PVPk30) on the membranes. Specifically, Brij35 primarily undergoes an adsorption-accumulation-penetration process; whereas PVPk30 exhibits a dynamic equilibrium between molecular adsorption-desorption and/or membrane permeation-healing competing mechanisms. This disparity in membrane action processes elucidates the discrepancy observed in their cytotoxicity during live cell experiments. The ability of photovoltage transient technology to investigate the entire membrane as a research subject along with its high sensitivity enables it to capture fluctuations in data points that reflect the coexistence of competitive mechanisms. Furthermore, photovoltage monitoring reveals the occurrence of peptide-induced membrane permeabilization. The distinct mechanism of action on the membrane between melittin (as a representative antimicrobial peptide) and TAT (a typical cell penetrating peptide) is elucidated. Finally, the conductive carbon dots (CDs) induced phenomena of membrane overcharging and overdischarging, are likely to be attributed to charge transfer between the silicon substrate and the embedded conductive CDs.&lt;/sec&gt;

Molecular mechanism of calcitriol enhances membrane water permeability

Helicobacter pylori (H. pylori) exhibits a unique membrane lipid composition, including dimyristoyl phosphatidylethanolamine (DMPE) and cholesterol, unlike other Gram-negative bacteria. Calcitriol has antimicrobial activity against H. pylori, but cholesterol enhances antibiotics resistance in H. pylori. This study explored the changes in membrane structure and the molecular mechanisms of cholesterol/calcitriol translocation using well-tempered metadynamics (WT-MetaD) simulations and microsecond conventional molecular dynamics (CMD) simulations. Calcitriol facilitated water transport across the membrane, while cholesterol had the opposite effect. The differing effects might result from the tail 25-hydroxyl group and a wider range of orientations of calcitriol in the DMPE/dimyristoyl phosphatidylglycerol (DMPG) (3:1) membrane. Calcitriol moves across the bilayer center without changing its orientation along the membrane Z-axis, becomes parallel to the membrane surface at the membrane-water interface, and then rotates approximately 90° in this interface. The translocation mechanism of calcitriol is quite different from the flip-flop of cholesterol. Moreover, calcitriol crossed from one layer to another more easily than cholesterol, causing successive perturbations to the hydrophobic core and increasing water permeation. These results improve our understanding of the relationship between cholesterol/calcitriol concentrations and the lipid bilayer structure and the role of lipid composition in water permeation.

Probing the Onset of the Bacterial Membrane Photodamage in Time using a Raman Optical Tweezer

Laser-induced photo damage of the optically confined microorganism is known to affect the bacterial membrane. We record the Raman spectra of a live, optically trapped Bacillus subtilis at different trapping time lapses to determine the changes in the bacterial membrane, which in turn impacts the flagellar rotation. A 1064 nm tightly focused laser traps a single de-flagellated bacterium and Surface Enhanced Raman Scattering (SERS) signals are recorded with silver nanoparticles (AgNPs) inserted into bacteria via the internal colloid method. The internal colloid method, albeit resulting in a modest signal increase, is employed in preference here to prevent undesirable cell aggregation or instabilities in trapping or compromised cell integrity resulting from the conventional nanoparticle dressing of the cell membrane. The second derivative of the Raman spectrum reveals subtle changes in the molecular structure of the bacterial membrane manifested by shifts in the phospholipid peak (1462 cm−1), amide III peak (1245 cm−1) and cytosine peak (792 cm−1), with increased trapping duration. This is followed by a Principal Component Analysis (PCA) to examine the changes occurring in the Raman spectral range (600 cm−1–1800 cm−1). By comparing the spectral shifts at specific time lapses from the moment of trapping, with the diminishing frequency of rotation of the body and flagella of the trapped flagellated counterpart bacterium at these same time lapses, we establish a direct correlation between the changes in membrane structure and compromised rotation of the bacterium during photodamage. Our results confirm that the subtle changes that occur at the biomolecular level in a cell when subjected to photodamage can be identified with good sensitivity, and moreover, that the changes occurring at the biomembrane have a role to play in reduced rotation of the trapped bacterium during exposure to the laser.

Advances in the study of exosome-derived miRNAs in the pathogenesis, diagnosis, and treatment of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an inflammatory disease caused by autoantibodies, with high morbidity and mortality. It involves multiple systems, particularly the renal, which can lead to lupus nephritis (LN); its multi-system effects have a significant impact on the physical and mental health of patients. Exosomes are vesicles that are secreted during cell activity and carry a variety of nucleic acids, proteins, and lipids. They are distributed through body fluids for cellular communication. MicroRNAs (miRNAs) are nucleic acids that are packaged within the exosome that are taken up and released in response to changes in plasma membrane structure. MiRNAs are potential participants in immune and inflammatory responses, which are transported to target cells and can inhibit gene expression in receptor cells. It has been suggested that exosomal miRNA can regulate the pathogenesis of SLE and, as such, they are of value in diagnosis and treatment. In this paper, we focus on the research progress into exosomal miRNA in SLE and inspire new directions for SLE related research.