Changes In Plasma Membrane Research Articles

Physiological characteristics of microbial transformation during chronic exposure to triclosan as a hydrophobic antibacterial agent and post-antibacterial cessation

ABSTRACT The use of triclosan (TCS) in hygiene products and other materials raises concerns about increased antimicrobial resistance. Research has shown that bacteria can develop resistance to TCS, but there is limited understanding of how bacterial behavior changes after TCS is removed. This study focuses on how bacteria adapt to prolonged TCS exposure and recover after its removal. It aims to improve practices for using antimicrobial agents in sanitation products and emphasize the importance of understanding exposure and recovery times to prevent resistance development. The study evaluated the bacterial behavior, determining the minimum inhibition concentration of TCS that 90% of Escherichia coli was inhibited (MIC90), predicting bacterial growth kinetics using the Modified Gompertz model and membrane permeability recovery. Bacteria showed a significant increase in resistance levels during exposure, with the MIC90 steadily increasing over 30 days and peaking at 16 mg/L. Upon removal, there was a notable 2-fold decrease in resistance after 10 days of reculturing in a non-chemical medium, likely due to restructuring changes in cell membranes. Therefore, in addition to reducing the occurrence of antibacterial agents in the environment, advanced treatments for eliminating antibacterial resistance should be performed on wastewater before being discharged into the environment.

Effect of Moderate Beer Intake on the Lipid Composition of Human Red Blood Cell Membranes.

Background/Objectives: Growing evidence suggests that erythrocyte membrane lipids are subject to changes during their lifespan. Factors such as the type of dietary intake and its composition contribute to the changes in red blood cell (RBC) membranes. Due to the high antioxidant content of beer, we aimed to investigate the effect of moderate beer consumption on the lipid composition of RBCs membranes from healthy overweight individuals. Methods: We conducted a four-weeks, prospective two-arm longitudinal crossed-over study, where participants (n = 36) were randomly assigned to alcohol-free beer group or traditional beer group. The lipids of RBCs membranes were assessed at the beginning and the end of the intervention by thin-layer chromatography. Results: Four-weeks of alcohol-free beer promoted changes in fatty acids (FA), free cholesterol (FC), phosphatidylethanolamine (PE) and phosphatidylcholine (PC) (p < 0.05). Meanwhile, traditional beer intake led to changes in FA, FC, phospholipids (PL), PE and PC (p < 0.05). The observed alterations in membrane lipids were found to be independent of sex and BMI as influencing factors. Conclusions: The lipid composition of erythrocyte membranes is distinctly but mildly influenced by the consumption of both non-alcoholic and conventional beer, with no effects on RBC membrane fluidity.

Diving into the metabolic interactions of titanium dioxide nanoparticles in “Sparus aurata” and “Ruditapes philippinarum”

The biological response to nanomaterials exposure depends on their properties, route of exposure, or model organism. Titanium dioxide nanoparticles (TiO2 NPs) are among the most used nanomaterials; however, concerns related to oxidative stress and metabolic effects resulting from their ingestion are rising. Therefore, in the present work, we addressed the metabolic effects of citrate-coated 45 nm TiO2 NPs combining bioaccumulation, tissue ultrastructure, and proteomics approaches on gilthead seabream, Sparus aurata and Japanese carpet shell, Ruditapes philippinarum. Sparus aurata was exposed through artificially contaminated feeds, while R. philippinarum was exposed using TiO2 NPs-doped microalgae solutions. The accumulation of titanium and TiO2 NPs in fish liver is associated with alterations in hepatic tissue structure, and alteration to the expression of proteins related to lipid and fatty acid metabolism, lipid breakdown for energy, lipid transport, and homeostasis. While cellular structure alterations and the expression of proteins were less affected than in gilthead seabream, atypical gill cilia and microvilli and alterations in metabolic-related proteins were also observed in the bivalve. Overall, the effects of TiO2 NPs exposure through feeding appear to stem from various interactions with cells, involving alterations in key metabolic proteins, and changes in cell membranes, their structures, and organelles. The possible appearance of metabolic disorders and the environmental risks to aquatic organisms posed by TiO2 NPs deserve further study.

Acrolein Induces Changes in Cell Membrane and Cytosol Proteins of Erythrocytes.

High concentrations of acrolein (2-propenal) are found in polluted air and cigarette smoke, and may also be generated endogenously. Acrolein is also associated with the induction and progression of many diseases. The high reactivity of acrolein towards the thiol and amino groups of amino acids may cause damage to cell proteins. Acrolein may be responsible for the induction of oxidative stress in cells. We hypothesized that acrolein may contribute to the protein damage in erythrocytes, leading to the disruption of the structure of cell membranes. The lipid membrane fluidity, membrane cytoskeleton, and osmotic fragility were measured for erythrocytes incubated with acrolein for 24 h. The levels of thiol, amino, and carbonyl groups were determined in cell membrane and cytosol proteins. The level of non-enzymatic antioxidant potential (NEAC) and TBARS was also measured. The obtained research results showed that the exposure of erythrocytes to acrolein causes changes in the cell membrane and cytosol proteins. Acrolein stiffens the cell membrane of erythrocytes and increases their osmotic sensitivity. Moreover, it has been shown that erythrocytes treated with acrolein significantly reduce the non-enzymatic antioxidant potential of the cytosol compared to the control.

Analysis of vibrational dynamics in cell-substrate interactions using nanopipette electrochemical sensors

Cell-substrate interaction plays a critical role in determining the mechanical status of living cell membrane. Changes of substrate surface properties can significantly alter the cell mechanical microenvironment, leading to mechanical changes of cell membrane. However, it is still difficult to accurately quantify the influence of the substrate surface properties on the mechanical status of living cell membrane without damage. This study addresses the challenge by using an electrochemical sensor made from an ultrasmall quartz nanopipette. With the tip diameter less than 100 nm, the nanopipette-based sensor achieves highly sensitive, noninvasive and label-free monitoring of the mechanical status of single living cells by collecting stable cyclic membrane oscillatory signals from continuous current versus time traces. The electrochemical signals collected from PC12 cells cultured on three different substrates (bare ITO (indium tin oxides) glass, hydroxyl modified ITO glass, amino modified ITO glass) indicate that the microenvironment more favorable for cell adhesion can increase the membrane stiffness. This work provides a label-free electrochemical approach to accurately quantify the mechanical status of single living cells in real-time, which may help to better understand the relationship between the cell membrane and the extra cellular matrix.

Antibacterial mechanism of ultrasound combined with thymol against Shewanella putrefaciens: implications for cell integrity and biofilm control

SummaryThe study aimed to assess the in vitro antibacterial effect of thymol (Thy) in conjunction with ultrasound (US) on Shewanella putrefaciens (S. putrefaciens). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Thy against S. putrefaciens were 0.50 and 1.00 mg mL−1, respectively. US was found to augment the antibacterial efficacy of Thy, resulting in a significant reduction of 2.36 log CFU mL−1 in the total colony count of S. putrefaciens, ensuring that the bacterial population maintained a consistently low growth rate. Quantitative detection of crystal violet revealed that the combined treatment exhibited a pronounced inhibitory effect on biofilm formation, with a clearance rate of mature biofilms reaching 91.60%. Alkaline phosphatase (AKPase), lactate dehydrogenase (LDHase), UV absorbing substance permeability, and other indicators were employed to measure changes in the bacterial cell membrane and internal environment. Scanning electron microscopy (SEM) was further used to observe the bacteria morphology before and after treated by US and Thy, a notable collapse of bacterial cells was observed, accompanied by ruptured outer membranes, damaged cell walls, and extensive leakage of cellular contents. This study presents a novel approach for controlling bacterial growth in food preservation methods.

Effect of different concentrations of oregano (&lt;i&gt;Origanum vulgare&lt;/i&gt;) extract on rumen digestion &lt;i&gt;in vitro&lt;/i&gt;

Residual antimicrobial substances resulting from the overuse of growth-promoting antibiotics in animal feed pose an emerging threat to human health and the environment. Plant extracts containing essential oils in general, and in particular Origanum vulgare extract, are a potential alternative to feed antibiotics, contributing to the growth of productive potential, due to their antimicrobial and antioxidant properties. They can inhibit the reproduction of pathogenic microorganisms, causing conformational changes in cell membranes. In this regard, the purpose of the study was to study the effect of different dosages of O. vulgare extract on the digestibility of diet components and the composition of volatile fatty acids in the rumen content under in vitro conditions. Three dosages of the oregano extract were tested in the experiment: 0.5; 1; 10 ml/l. The results of the present study indicate that small doses of O. vulgare extract do not lead to metabolic shifts in the rumen digestion. High dose (10 ml/l), on the contrary, reduces the total number of protozoa. The average dose load of 1 ml/l leads to an increase in digestibility to 72.63% and the concentration of infusoria to 555.56 thousand pcs/ml. Thus, based on the results obtained, it follows that the inclusion of the O. vulgare extract in a dose of 1 ml/l enhances metabolic processes in the rumen, leading to better digestion of feed. The dosage of 10 ml/l, the maximum of the tested, provided an increase in the concentration of the volatile fatty acids. However, when using 1 ml/l of O. vulgare, the most significant changes in the concentration of the volatile fatty acids occurred.

Microviscosity of tumor cell membranes

Oncologic diseases occupy the second line in the structure of patient mortality in the world. Thus, the development of new and improvement of existing methods of treatment of oncologic diseases, search for new targets for chemopreparations is an urgent task. Cell membrane can serve as a targeting target for therapy, as it is the first barrier for chemopreparations. Changes in biophysical parameters of the plasma membrane, including viscosity, play an essential role in the development of pathological states of the organism.&#x0D; Despite the fundamental importance of viscosity for cell vital activity, this parameter remains poorly studied and its role in disease pathogenesis and response to therapy is not completely clear. Tumor cell membrane viscosity determines the degree of malignancy, metastasis potential, origin of cancer cells, and differs significantly from their normal counterparts. Also, membrane viscosity changes in the process of induction of drug resistance and differs between sensitive tumor cells and their resistant counterparts, i.e. plasma membrane viscosity can serve as a diagnostic indicator.&#x0D; Viscosity changes in tumor cell membranes directly depend on their lipid composition of the plasma membrane. Different content of certain lipids in the plasma membrane, in particular, cholesterol, plays an essential role in the formation of targets for chemopreparations, their localization inside the membrane and penetration inside the tumor cell. The lipid composition of the plasma membrane is also altered during chemotherapy and during the induction of drug resistance. Accordingly, the altered lipid composition of the membrane may serve as a prognostic criterion for tumor response to chemotherapy.&#x0D; Based on the analysis of the state of research in the field of tumor cell viscosity studies, it was revealed that it is an urgent task to study the role of membrane viscosity in the process of oncogenesis and its changes in the course of therapeutic action. Studies in this direction are of interest for the development of new therapeutic approaches and individualization of treatment.

Anti-Biofilm Activity of Cocultimycin A against Candida albicans

Candida albicans (C. albicans), the most common fungal pathogen, has the ability to form a biofilm, leading to enhanced virulence and antibiotic resistance. Cocultimycin A, a novel antifungal antibiotic isolated from the co-culture of two marine fungi, exhibited a potent inhibitory effect on planktonic C. albicans cells. This study aimed to evaluate the anti-biofilm activity of cocultimycin A against C. albicans and explore its underlying mechanism. Crystal violet staining showed that cocultimycin A remarkably inhibited biofilm formation in a dose-dependent manner and disrupted mature biofilms at higher concentrations. However, the metabolic activity of mature biofilms treated with lower concentrations of cocultimycin A significantly decreased when using the XTT reduction method. Cocultimycin A could inhibit yeast-to-hypha transition and mycelium formation of C. albicans colonies, which was observed through the use of a light microscope. Scanning electron microscopy revealed that biofilms treated with cocultimycin A were disrupted, yeast cells increased, and hypha cells decreased and significantly shortened. The adhesive ability of C. albicans cells treated with cocultimycin A to the medium and HOEC cells significantly decreased. Through the use of a qRT-PCR assay, the expression of multiple genes related to adhesion, hyphal formation and cell membrane changes in relation to biofilm cells treated with cocultimycin A. All these results suggested that cocultimycin A may be considered a potential novel molecule for treating and preventing biofilm-related C. albicans infections.

Investigation of cell damage of periodontopathic bacteria exposed to silver, zirconium oxide, and silicon oxide nanoparticles as antibacterial agents

AbstractAntibiotic resistance is one of the biggest public health problems of our time. The nanoparticles are a powerful alternative to these antibiotics. Engineered nanoparticles show toxic effects on bacteria by different mechanisms. The bacteria–cell interaction of engineered nanoparticles exerts their toxic effects through changes in cell wall, cell membrane, and cytoplasm content/density. Thus, death occurs as a result of cell deformation. In this study, the cellular damage of silver nanoparticles, which are known to have strong antibacterial properties, and zirconium oxide and silicon oxide engineering nanoparticles, which are less known, on periodontopathic (Prevotella intermedia and Aggregatibacter actinomycetemcomitans) bacteria, were investigated by ultrastructural changes. The lysis of the cytoplasm and separation of the membrane cytoplasm were observed. Both types of bacteria treated with Ag ENP show more hollow cytoplasm than bacteria treated with the other two nanoparticles.

Puncturing lipid membranes: onset of pore formation and the role of hydrogen bonding in the presence of flavonoids

Products of lipid peroxidation induce detrimental structural changes in cell membranes, such as the formation of water pores, which occur in the presence of lipids with partially oxidized chains. However, the influence of another class of products, dicarboxylic acids, is still unclear. These products have greater mobility in the lipid bilayer, which enables their aggregation and the formation of favorable sites for the appearance of pores. Therefore, dodecanedioic acid (DDA) was selected as a model product. Additionally, the influence of several structurally different flavonoids on DDA aggregation via formation of hydrogen bonds with carboxyl groups was investigated. The molecular dynamics of DDA in DOPC lipid bilayer revealed the formation of aggregates extending over the hydrophobic region of the bilayer and increasing its polarity. Consequently, water penetration and the appearance of water wires was observed, representing a new step in the mechanism of pore formation. Furthermore, DDA molecules were found to interact with lipid polar groups, causing them to be buried in the bilayer. The addition of flavonoids to the system disrupted aggregate formation, resulting in the displacement of DDA molecules from the center of the bilayer. The placement of DDA and flavonoids in the lipid bilayer was confirmed by small-angle X-ray scattering. Atomic force microscopy and electron paramagnetic resonance were used to characterize the structural properties. The presence of DDA increased bilayer roughness and decreased the ordering of lipid chains, confirming its detrimental effects on the membrane surface, while flavonoids were found to reduce or reverse these changes.

Concentration-dependent mechanism of the binding behavior of ibuprofen to the cell membrane: A molecular dynamic simulation study

Ibuprofen is a commonly used drug for treating headaches, pain, and fever. The lipid bilayer is the primary and most important interface for drugs to interact with biological systems. However, the molecular interactions between ibuprofen and the cell membrane are not well understood. Our findings suggest that the interactions between ibuprofen and the bilayer involve multiple steps and depend on the concentration of the drug. At low concentrations of ibuprofen, it can bind to the surface of the lipid bilayer. The electrostatic and vdW energies of IBU-lipid at 0 ns of the simulation were −22.5 ± 3.2 and −5.9 ± 1.2 kj.mol-1 Fig. 2. In the following, the vdW energy of the IBU-lipid was increased by around −134.6 ± 3.7 kj.mol-1 whereas the electrostatic energy of the IBU-lipid was significantly decreased. This binding is facilitated by electrostatic and vdW interactions between ibuprofen and the head group of lipids. In the second step, ibuprofen is inserted into the lipid bilayer and positioned at the interface between the bilayer and the aqueous phase. In high concentrations of ibuprofen, it moved to the central region of the lipid bilayer. At this concentration, the physical and structural properties of the cell membrane change significantly. Results from the radial distribution function analysis indicate that at low concentrations, ibuprofen molecules are situated close to the head groups of phosphate groups. However, at high concentrations of ibuprofen, these molecules move to the inner side of the lipid bilayer. In addition, our findings indicate that at low concentrations of ibuprofen, these molecules did not significantly alter the physical properties of the cell membrane. In contrast, at high concentrations of ibuprofen, the physical parameters of the hydrocarbon tails, such as thickness, fluidity, and order, changed dramatically. APL parameter for POPC membrane increased slightly to 0.60 and 0.63 nm2 in the presence of low and high concentrations of ibuprofen molecules. The three-step interaction between ibuprofen and the lipid bilayer involves several events, such as the movement of ibuprofen molecules towards the central region of the lipid bilayer and the deformation and alteration of the structural and stability properties of the cell membrane. These effects are observed only at high concentrations of ibuprofen. It appears that the side effects of ibuprofen overdose are related to changes in the properties of the cell membrane and, subsequently, the function of membrane-anchored target proteins.

Influence of CoOx surface passivation and Sn/Zr-co-doping on the photocatalytic activity of Fe2O3 nanorod photocatalysts for bacterial inactivation and photo-Fenton degradation

Hydrothermal and wet impregnation methods are presented in this study for synthesizing CoOx(1 wt%)/Sn/Zr-codoped Fe2O3 nanorod photocatalysts for the degradation of organic pollutants and deactivation of bacteria. A hydrothermal route was used to synthesize self-assembled rod-like hierarchical structures of Sn(0–6%) doped Zr–Fe2O3 NRs. Additionally, a wet impregnation method was used to load CoOx onto the surface of photocatalysts (Sn(0–6%)-doped Zr–Fe2O3 NRs). A series of 1 wt% CoOx modified Sn(0–6%)-doped Zr–Fe2O3 NRs were synthesized, characterized, and utilized for the photocatalytic decomposition of organic contaminants, along with the killing of E. coli and S. aureus. In comparison with 0, 2, and 6% Sn co-doped Zr–Fe2O3 NRs, the CoOx(1 wt%)/4%Sn/Zr–Fe2O3 NRs photocatalyst exhibited an E. coli and S. aureus inactivation efficiencies (90 and 98%). A bio-TEM study of treated and untreated bacterial cells revealed that the CoOx(1 wt%)/4%Sn/Zr–Fe2O3 NRs photocatalyst led to considerable changes in the bacterial cell membranes’ morphology. The optimal CoOx(1 wt%)/Sn(4%) co-doped Zr–Fe2O3 NRs photocatalyst achieved degradation efficiencies of 98.5% and 94.6% for BPA and orange II dye, respectively. As a result, this work will provide a facile and effective method for developing visible light-active photocatalysts for bacterial inactivation and organic pollutants degradation.

Breaking Down Tumor Drug Resistance: The Link Between Cell Membrane Changes and Treatment Efficacy

Abstract There have been significant advances in our understanding of how changes in the fluidity and permeability of the cell membrane can affect drug resistance in cancer. Research has shown that cancer cells often have changes in the fluidity and permeability of their cell membrane that contribute to their resistance to drugs used to treat cancer. These changes may be due to changes in the composition and organization of the lipid bilayer that makes up the membrane, as well as changes in the expression or localization of proteins and other molecules embedded in the membrane. The lipid composition in the tumor cell membrane changes with drug resistance, which can affect the fluidity and permeability of the cell membrane. Reversal of drug resistance can be achieved by altering cell membrane fluidity and permeability. In recent years, there have been numerous studies aimed at understanding the mechanisms underlying these changes and identifying strategies to overcome drug resistance in cancer. This research has led to the development of new drugs and drug delivery systems that are designed to target specific changes in the cell membrane of cancer cells and improve the effectiveness of chemotherapy. Overall, the advances in our understanding of the role of cell membrane fluidity and permeability in drug resistance in cancer have led to the development of new approaches to treat cancer and improve patient outcomes and further research is needed to continue to improve the understanding of these mechanisms and to identify new strategies to overcome drug resistance in cancer. This article highlights the research status and detection methods of cell membrane fluidity and permeability affecting tumor drug resistance.

Behavior and linkage mechanism of extracellular polymers, cell membrane peroxides and intracellular peroxidases during high concentration vaporized hydrogen peroxide sterilization

Vaporized hydrogen peroxide (VHP) sterilization has been widely used in the fields of medical care and pharmaceuticals. Extracellular polymeric substances (EPS) connected tightly to the cell membrane is first barrier that must be broken through, and less is known about direct change of cell membrane peroxides, and the linkage mechanism among EPS, cell membrane and intracellular damages is still unclear during high concentration VHP sterilization. After optimizing the VHP sterilization process of specific drug-packaging equipment based on the sterility assurance level of 10−6 cfu, we studied the degradation kinetics of exopolysaccharide, exoprotein, extracellular DNA, and investigated the changes of cell membrane lipid/protein peroxides and intracellular peroxidases, and discussed the linkage mechanism of microbial EPS, cell membrane and intracellular damages during high concentration VHP sterilization. The results indicated: (1) The order of degradation kinetics of microbial EPS was exopolysaccharide > exoprotein > extracellular DNA, it was the key to achieve fast and effective VHP sterilization that sufficient high concentration VHP (>400 ppm) was adopted to rapidly destroy EPS (>20 min), resulting in the serious destruction of proteins and lipids of cell membrane; (2) The key mechanism of short time sterilization using high concentration VHP was that the serious loss of the structure/function of cell membrane was the most fatal but the damage of intracellular enzymes and DNA was limited for bacterial cell living.

Drug Resistance Mechanism and Detection Method of Salmonella

As an important zoonotic food-borne pathogen, Salmonella is a concern for public health authorities. In particular, bacteria that are resistant to multiple antimicrobials can confuse the efficacy of treatment for infectious diseases. Drug-resistant bacteria have a variety of drug-resistant molecular and cellular mechanisms. These antimicrobial resistance mechanisms include antibiotic efflux, permeability changes in cell membranes, enzymatic drug inactivation, biofilm formation, drug target changes, and protection of antimicrobial targets. In this paper, the mechanisms of antimicrobial resistance in salmonella and the techniques of detecting antibiotic resistance by traditional and molecular methods are reviewed, with emphasis on their advantages and disadvantages, as well as the validity and reliability of the results.

Artificial Cells for Cellular Behavior Mimicry Induced by Sphingomyelin Degradation.

Sphingomyelinase (SMase), a hydrolase of sphingomyelin (SM) enriched in the outer leaflet of the plasma membrane of mammalian cells, is closely associated with the onset and development of many diseases, but the specific mechanisms of SMase on the cell structure, function, and behavior are not yet fully understood due to the complexity of the cell structure. Artificial cells are minimal biological systems constructed from various molecular components designed to mimic cellular processes, behaviors, and structures, which are excellent models for studying biochemical reactions and dynamic changes in cell membranes. In this work, we presented an artificial cell model that mimics the lipid composition and content of the outer leaflet of mammalian plasma membranes for studying the effect of SMase on cell behavior. The results confirmed that the artificial cells can respond to SM degradation by producing ceramides that enrich and alter the membrane charge and permeability, thus inducing the budding and fission of the artificial cells. Thus, the artificial cells developed here provide a powerful tool to study the mechanism of action of cell membrane lipids on cell biological behavior, paving the way for further molecular mechanism studies.

Epoxy Triglyceride Enhances Intestinal Permeability via Caspase-1/NLRP3/GSDMD and cGAS-STING Pathways in Dextran Sulfate Sodium-Induced Colitis Mice.

Oxidized triglyceride monomers are the main cytotoxic products of deep-frying oil. However, its impact on the intestinal barrier, the first health guardian, remains unknown. In this study, HPLC-MS/MS analysis revealed that the epoxy group is the main oxidation product, indicating that it may be the main cytotoxic factor. Therefore, 1-9,10-epoxystearic ester, 2,3-dioleic acid (EGT) and glycerol trioleate (GT) were used to reveal the effect of the epoxy group on the intestinal barrier of dextran sulfate sodium-induced colitis. Characteristics analysis showed that EGT could aggravate intestinal damage. The relative mRNA expression analysis suggested that EGT could activate Caspase-1/NLRP3/GSDMD, thereby inducing pyroptosis. The proinflammatory cytokines activated by pyroptosis and the cGAS-STING pathway were released through the pores, thus inducing the disintegration of the tight junction between the intestinal epithelial cells and enhancing intestinal permeability. Metabonomics further confirmed that EGT can change the composition and content of phospholipids on the cell membrane, indicating the morphological changes of the intestinal epithelial cell membrane. In conclusion, this study highlights that EGT induced intestinal dysfunction via Caspase-1/NLRP3/GSDMD and cGAS-STING pathways.

NRXN1 depletion in the medial prefrontal cortex induces anxiety-like behaviors and abnormal social phenotypes along with impaired neurite outgrowth in rat

BackgroundNeurodevelopmental disorders (NDDs) are a group of disorders induced by abnormal brain developmental processes. The prefrontal cortex (PFC) plays an essential role in executive function, and its role in NDDs has been reported. NDDs are associated with high-risk gene mutations and share partially overlapping genetic abnormalities.MethodsNeurexins (NRXNs) are related to autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). NRXN1, an essential susceptibility gene for NDDs, has been reported to be associated with NDDs. However, little is known about its key role in NDDs.ResultsNRXN1 downregulation in the medial PFC induced anxiety-like behaviors and abnormal social phenotypes with impaired neurite outgrowth in Sh-NRXN1 in prefrontal neurons. Moreover, tandem mass tag (TMT)-based proteomic analysis of rat brain samples showed that NRXN1 downregulation led to significant proteome alterations, including pathways related to the extracellular matrix, cell membrane, and morphologic change. Furthermore, full-automatic immunoblotting analysis verified the differently expressed proteins related to cell morphology and membrane structure.ConclusionsOur results confirmed the association of NRXN1 with abnormal behaviors in NDDs and provided richer insights into specific prefrontal knockdown in adolescence, potentially expanding the NRXN1 interactome and contributing to human health.Graphical abstract

Microscopic springs: Investigating viscoelastic and elastic tendencies of the cell membrane.

Cell membranes are normally thought of as viscoelastic materials because they exhibit both viscous and elastic properties when deforming, however, some researchers describe membranes as elastic only. Our project seeks to quantify the membrane deformations during a splitting event, and mathematically predict membrane tensions if it were an elastic or viscoelastic material. Knowing the mechanical description that is most appropriate can help future research interested in describing cell mechanics when cells split, change shape, or move. First, we quantified cell shape from experimental fluorescently dyed membranes using ImageJ. We assume that knowing the physical location of the cell membrane over time can be used to quantify how the cell membrane changes due to forces acting on/in the membrane. We built MATLAB functions to import coordinates from ImageJ, center them, segment them based on arctan values into specific angle quadrants, and calculate the force the membrane experiences based on its location relative to its angular quadrant when considered an elastic spring or viscoelastic material. Centering the coordinates allows the functions to apply to multiple different cell experiments, while quadrants allowed the accounting of localized growth and shrinkage of the membrane. To model the elastic properties, we used a Hooke's Law spring equation and a viscoelastic equation with elastic and damper components. Our results suggest that the cell membrane can be treated as a viscoelastic material under small time scales (< 3 minutes) and as an elastic spring for larger time scale deformations. These results can be validated experimentally through laser ablation. By ablating a hole in the cell membrane, we can quantify the recoil of the membrane to determine how much tension was present before the ablation and compare the scale of the experimental tension with our model predicted tension.