Membrane Lipid Fluidity Research Articles

Orchestrated desaturation reprogramming from stearoyl-CoA desaturase to fatty acid desaturase 2 in cancer epithelial-mesenchymal transition and metastasis.

Adaptative desaturation in fatty acid (FA) is an emerging hallmark of cancer metabolic plasticity. Desaturases such as stearoyl-CoA desaturase (SCD) and fatty acid desaturase 2 (FADS2) have been implicated in multiple cancers, and their dominant and compensatory effects have recently been highlighted. However, how tumors initiate and sustain their self-sufficient FA desaturation to maintain phenotypic transition remains elusive. This study aimed to explore the molecular orchestration of SCD and FADS2 and their specific reprogramming mechanisms in response to cancer progression. The potential interactions between SCD and FADS2 were explored by bioinformatics analyses across multiple cancer cohorts, which guided subsequent functional and mechanistic investigations. The expression levels of desaturases were investigated with online datasets and validated in both cancer tissues and cell lines. Specific desaturation activities were characterized through various isomer-resolved lipidomics methods and sensitivity assays using desaturase inhibitors. In-situ lipid profiling was conducted using multiplex stimulated Raman scattering imaging. Functional assays were performed both in vitro and in vivo, with RNA-sequencing employed for the mechanism verification. After integration of the RNA-protein-metabolite levels, the data revealed that a reprogramming from SCD-dependent to FADS2-dependent desaturation was linked to cancer epithelial-mesenchymal transition (EMT) and progression in both patients and cell lines. FADS2 overexpression and SCD suppression concurrently maintained EMT plasticity. A FADS2/β-catenin self-reinforcing feedback loop facilitated the degree of lipid unsaturation, membrane fluidity, metastatic potential and EMT signaling. Moreover, SCD inhibition triggered a lethal apoptosis but boosted survival plasticity by inducing EMT and enhancing FA uptake via adenosine monophosphate-activated protein kinase activation. Notably, this desaturation reprogramming increased transforming growth factor-β2, effectively sustaining aggressive phenotypes and metabolic plasticity during EMT. These findings revealed a metabolic reprogramming from SCD-dependent to FADS2-dependent desaturation during cancer EMT and progression, which concurrently supports EMT plasticity. Targeting desaturation reprogramming represents a potential vulnerability for cancer metabolic therapy.

Effect of Ionic and Nonionic Compounds Structure on the Fluidity of Model Lipid Membranes: Computer Simulation and EPR Experiment.

This article investigates the influence of dopant molecules on the structural and dynamic properties of lipid bilayers in liposomes, with a focus on the effects of dopant concentration, size, and introduced electric charge. Experimental studies were performed using electron paramagnetic resonance (EPR) spectroscopy with spin probes, complemented by Monte Carlo simulations. Liposomes, formed via lecithin sonication, were doped with compounds of varying concentrations and analyzed using EPR spectroscopy to assess changes in membrane rigidity. Parallel simulations modeled the membrane's surface layer as a system of electric dipoles on a 20 × 20 rectangular matrix. As in the EPR experiments, the simulation explored the effects of dopant molecules differing in size and charge, while gradually increasing their concentrations in the system. Minimum binding energy configurations were determined from the simulations. The results revealed a strong correlation between the EPR data and simulation outcomes, indicating a clear dependence of membrane stiffening on the concentration, size, and charge of dopant molecules. This effect was most pronounced at low dopant concentrations (~1-1.5% for q = 2 and 1.5-2% for q ≥ 3). No significant stiffening was observed for neutral molecules lacking charge. These findings offer valuable insights into the mechanisms of membrane modulation by dopants and provide a quantitative framework for understanding their impact on lipid bilayer properties.

Cm-p5, a molluscan-derived antifungal peptide exerts its activity by a membrane surface covering in a non-penetrating mode

Amidst the health crisis caused by the rise of multi-resistant pathogenic microorganisms, Antimicrobial Peptides (AMPs) have emerged as a potential alternative to traditional antibiotics. In this sense, Cm-p5 is an AMP with fungistatic activity against the yeast Candida albicans. Its antimicrobial activity and selectivity have been well characterized; however, the mechanism of action is still unknown. This study used biophysical approaches to gain insight into how this peptide exerts its activity. Stability and fluidity of lipid membrane were explored by liposome leakage and Laurdan generalized polarization (GP) respectively, suggesting that Cm-p5 does not perturb lipid membranes even at very high concentrations (≥100µm.L-1). Likewise, no depolarizing action was observed using 3,3'-propil-2,2'-thyodicarbocianine, a potential membrane fluorescent reporter, with C. albicans cells or the corresponding liposome models. Changes in liposome size were analyzed by Dynamic Light Scattering (DLS) data, indicating that Cm-p5 covers the vesicular surface slightly increasing liposome hydrodynamic size, without liposome rupture. These results were further corroborated with Langmuir monolayer isotherms, where no significant changes in lateral pressure or area per lipid were detected, indicating little or no insertion. Finally, data obtained from molecular dynamics simulations aligned with in vitro observations, whereby Cm-p5 slightly interacted with the fungal membrane model surface without causing significant perturbation. These results suggest Cm-p5 is not a pore-forming anti-fungal peptide and that other mechanisms of action on the membrane as some limitation of fungal nutrition or receptor-dependent transduction for depressing growth development should be explored.

Exploring pH-Triggered Lamellar to Cubic Phase Transition in 2-Hydroxyoleic Acid/Monoolein Nanodispersions: Insights into Membrane Physicochemical Properties.

Self-assembled lipid nanoparticles (LNPs) are essential nanocarriers for drug delivery. Functionalization of LNPs with ionizable lipids creates pH-responsive nanoparticles that change structures under varying pH conditions, enabling pH-triggered drug release. Typically, bicontinuous cubic phase nanoparticles (Cubosomes) and lamellar structured vesicles (Liposomes) differ in lipid packing statuses, affecting drug release and cellular uptake. However, most research predominantly focuses on elucidating lattice structure changes of these LNPs without a deep investigation of lipid-membrane properties. Addressing this gap, our study delves into the lipid-membrane physicochemical property variations during the lamellar-to-cubic phase transition. Here, we prepared pH-responsive LNPs using 2-hydroxyoleic acid/monoolein (2-OHOA/MO) binary components. Small-angle X-ray scattering (SAXS) revealed a phase transition from lamellar vesicles (Lα) to cubosomes (Im3m/Pn3m) with pH reduction. Laurdan and 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence probes tracked the lipid-water interfacial polarity and lipid-membrane fluidity variations during the phase transition. Raman spectroscopy provided further insights into lipid-membrane lipid chain packing and chain torsion. We observed that the changes in lipid-membrane properties coincided with the lamellar-to-cubic phase transition, emphasizing the interplay between the phase structure and lipid-membrane behaviors in the 2-OHOA/MO system. This study provides insights into the lipid-membrane properties variation during the pH-triggered phase transition in the 2-OHOA/MO system, guiding future research toward more effective and reliable pH-responsive drug delivery platforms.

Masks As a New Hotspot for Antibiotic Resistance Gene Spread: Reveal the Contribution of Atmospheric Pollutants and Potential Risks.

The consumption of disposable surgical masks (DSMs) considerably increased during the coronavirus pandemic in 2019. Herein, we explored the spread of antibiotic resistance genes (ARGs) and the potential risks of antibiotic resistant bacteria (ARB) on DSMs. At environmentally relevant concentrations, the conjugate transfer frequency (CTF) of ARGs increased by 1.34-2.37 folds by 20 μg/m3 of atmospheric water-soluble inorganic ions (WSIIs), and it increased by 2.62-2.86 folds by 80 ng/m3 of polycyclic aromatic hydrocarbons (PAHs). Total suspended particulates (TSP) further promoted the CTF in combination with WSIIs or PAHs. Under WSII and PAH exposure, gene expression levels related to oxidative stress, cell membrane, and the adenosine triphosphate (ATP) were upregulated. WSIIs predominantly induced cellular contact, while PAHs triggered ATP formation and membrane damage. Molecular dynamics simulations showed that WSIIs and PAHs reduced membrane lipid fluidity and increased membrane permeability through interactions with the phosphatidylcholine bilayer. DSM filtering performance decreased, and the CTF of ARGs increased with the wearing time. The gut simulator test showed that ARB disrupted the human gut microbial community and increased total ARG abundance but did not change the ARG abundance carried by ARB themselves. A mathematical model showed that long-term WSII and PAH exposure accelerated ARG dissemination in DSMs.

The diffuse interface description of fluid lipid membranes captures key features of the hemifusion pathway and lateral stress profile.

Topological transitions of lipid membranes are ubiquitous in key biological processes for cell life, like neurotransmission, fertilization, morphogenesis, and viral infections. Despite this, they are not well understood due to their multiscale nature, which limits the use of molecular models and calls for a mesoscopic approach such as the celebrated Canham-Helfrich one. Unfortunately, such a model cannot handle topological transitions, hiding the crucial involved forces and the appearance of the experimentally observed hemifused intermediates. In this work, we describe the membrane as a diffuse interface preserving the Canham-Helfrich elasticity. We show that pivotal features of the hemifusion pathway are captured by this mesoscopic approach, e.g. a (meta)stable hemifusion state and the fusogenic behavior of negative monolayer spontaneous curvatures. The membrane lateral stress profile is calculated as a function of the elastic rigidities, yielding a coarse-grained version of molecular models findings. Insights into the fusogenic mechanism are reported and discussed.

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.

The Metabolism, Detrimental Effects, and Signal Transduction Mechanism of Reactive Oxygen Species in Plants under Abiotic Stress

Plants are a major source of bio based materials, and their productivity is significantly impacted by environmental adversities with the continuous deterioration of the environment. The disruption of reactive oxygen species (ROS) production and scavenging balance is a common consequence of various abiotic stresses in plants, resulting in the excessive accumulation of ROS. However, it is crucial to acknowledging the dual role of ROS, acting both as harmful substances and signaling molecules. ROS can interact with membrane proteins, initiating a chain reaction of membrane lipid peroxidation. This process leads to a decrease in membrane lipid unsaturation and fluidity, as well as an increase in membrane permeability. Inhibited enzyme activity even lead to loss of protein function, caused DNA damage and mutations, blocked DNA replication and transcription, eventually leading to cell death. This can result in significant reductions in crop yield and biomass in bio based agricultural production. ROS also played vital role in signal molecule transduction in the process of plant resistance to stress, and worked in concert with other signal molecules to induce the stress resistance genes’ expression and enhance plant resistance. Hereto, scavenging mechanism for ROS in plants is of the essence to regulate the concentration of ROS, thus determining which role ROS play. The thermal dissipation of excess light energy effectively avoids ROS production, and the enzymatic and non-enzymatic antioxidant defense systems in plants work cooperatively to clear excessive ROS. This review provides a comprehensive summary of the production pathway, detrimental effects, scavenging mechanism and signal transduction of ROS in plants under abiotic stress.

Shear-Induced Nonequilibrium Patterns in Lipid Bilayer Membranes Exhibiting Phase Separation.

The nonequilibrium dynamics of a fluid lipid membrane under external stimuli is an important issue that spans disciplines such as soft matter, biophysical chemistry, and interface science. This study investigated the dynamic response of lipid vesicles with order-disorder phase separation, which mimics a plasma membrane heterogeneity, to shear flow. Lipid vesicles were immobilized in a microfluidic chamber, and shear-induced nonequilibrium patterns on the membrane surface were observed by an optical microscope. We found that phase-separated membranes exhibit a dissipative structure of stripe patterns along the vortex flow on the membrane surface, and the number of stripes increased with the flow rate. At a high flow rate, the membrane exhibited a stripe-to-wave transition, where striped domains often migrated and the replacement of two different phases happened at vortex centers with time. We obtained a dynamic phase diagram of the shear-induced wave pattern by changing the flow rate, membrane components, and temperature. These findings could provide insight into the dissipative structures of lipid membranes out of equilibrium and flow-mediated mechanotransduction of biological membranes.

Exploring the Physical Properties of Lipid Membranes with Polyhydroxy Oxanorbornane Head Group Using NBD-Conjugated and DPH Fluorescent Probes.

The present study focuses on exploring the physical properties of lipid membranes based on the polyhydroxy oxanorbornane (PH-ONB) headgroup, designed as synthetic analogues of naturally occurring archaeal lipid membranes. Specifically, we study two variants of PH-ONB headgroup-based lipids differing in the number of hydroxy groups present in the headgroup, with one having two hydroxy groups (ONB-2OH) and the other having three (ONB-3OH). These lipids form stable bilayer membranes. The study begins with a comprehensive analysis of the fluorescence characteristics of nitrobenzoxadiazole (NBD)-tagged ONB-based lipids in different solvent environments and within a model lipid membrane 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Subsequently, the physical properties of the ONB-based membranes were examined by using an NBD-tagged ONB-based probe and a commonly used extrinsic 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescent probe. The steady-state and time-resolved fluorescence properties of the NBD-tagged ONB-based probe and DPH were used to compare the physical properties of the ONB-based membranes, including polarity, fluidity, phase transition, order, hydration, location, heterogeneity, and rotational diffusion. The solid gel to liquid crystalline phase transition temperatures of ONB-2OH and ONB-3OH lipid membranes are found to be (68 ± 1) °C and (74 ± 1) °C, respectively. The variation in organization (size), fluidity, and phase transition temperature of ONB-based lipid membranes is explained by the extent of hydrogen bonding interactions between lipid head groups. ONB-based membranes exhibit characteristics similar to those of phospholipid membranes and possess a notably high phase transition temperature. These properties make them a promising and cost-effective synthetic alternative to archaeal lipid membranes with a wide range of potential applications.

Effects of grafted polymers on the lipid membrane fluidity

Since the membrane fluidity controls the cellular functions, it is important to identify the factors that determine the cell membrane viscosity. Cell membranes are composed of not only lipids and proteins but also polysaccharide chain-anchored molecules, such as glycolipids. To reveal the effects of grafted polymers on the membrane fluidity, in this study, we measured the membrane viscosity of polymer-grafted giant unilamellar vesicles (GUVs), which were prepared by introducing the poly (ethylene glycol) (PEG)-anchored lipids to the ternary GUVs composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and cholesterol. The membrane viscosity was obtained from the velocity field on the GUV generated by applying a point force, based on the hydrodynamic model proposed by Henle and Levine. The velocity field was visualized by a motion of the circular liquid ordered (Lo) domains formed by a phase separation. With increasing PEG density, the membrane viscosity of PEG-grafted GUVs increased gradually in the mushroom region and significantly in the brush region. We propose a hydrodynamic model that includes the excluded volume effect of PEG chains to explain the increase in membrane viscosity in the mushroom region. This work provides a basic understanding of how grafted polymers affect the membrane fluidity.

Evaluation of the passive permeability of antidepressants through pore-suspended lipid bilayer

HypothesisThe antidepressant drug imipramine, and its metabolite desipramine show different extents of interaction with, and passive permeation through, cellular membrane models, with the effects depending on the membrane composition. Through multimodal interrogation, we can observe that the drugs have a direct impact on the physicochemical properties of the membrane, that may play a role in their pharmacokinetics. ExperimentsMicrocavity pore-suspended lipid bilayers (MSLBs) of four different compositions, each with a different headgroup charge namely; zwitterionic dioleoylphosphatidylcholine (DOPC), mixed DOPC and negatively charged dioleoylphosphatidylglycerol (DOPG) (3:1), mixed DOPC and positively charged dioleoyltrimethylammoniumpropane (DOTAP) (3:1), and with increasing complex composition mimicking blood-brain-barrier (BBB) were prepared on gold and polydimethylsiloxane (PDMS) substrates using a Langmuir-Blodgett-vesicle fusion method. The molecular interaction and permeation of antidepressants, imipramine, and its metabolite desipramine with the lipid bilayers were evaluated using highly sensitive label-free electrochemical impedance spectroscopy (EIS) and surface-enhanced Raman spectroscopy (SERS). Drug-induced membrane packing/fluidity alterations were assessed using fluorescence lifetime imaging (FLIM) and fluorescence lifetime correlation spectroscopy (FLCS) of MSLB over microfluidic PDMS array. FindingsUsing EIS to evaluate in real-time membrane admittance changes, we found that imipramine greatly increases the ion permeability of negatively charged DOPC:DOPG (3:1) membranes. The effect was observed also at neutral (DOPC) and to a lesser extent at positively charged DOPC:DOTAP(3:1) membranes. In contrast, desipramine had a much weaker impact on ion permeability across all bilayer compositions. Temporal capacitance data show that desipramine intercalates at negatively charged membrane thereby increasing the thickness of the membrane. The overall kinetics of the imipramine permeation is higher than that of desipramine. This was confirmed using SERS, which also provides an evaluation of drug passive permeation based on arrival time across the membrane. Using FLCS, we found that imipramine increases the lipid membrane fluidity, whereas desipramine lowers it, with the exception of the negatively charged membrane. A translocation rate pharmacokinetics model was established for the first time at the MSLB platform by real-time monitoring of the variation in membrane resistance of pristine DOPC and blood-brain-barrier (BBB) membrane.

Abstract 16909: Eicosapentaenoic Acid and Docosahexaenoic Acid Have Competing Effects on Membrane Lipid Dynamics Due to Differences in Structure

Background: Omega-3 fatty acids (n3-FAs) incorporate into vascular cell membranes where they modulate protein function and signal transduction. The n3-FA eicosapentaenoic acid (EPA) delivered in ethyl ester form (icosapent ethyl) reduced a broad range of cardiovascular events in high-risk patients (REDUCE-IT). This was not observed with mixed n3-FA formulations containing docosahexaenoic acid (DHA) in STRENGTH and other trials. These discordant outcomes indicate DHA may counter certain EPA effects due to its additional carbons and double bond. We compared these n3-FA effects on membrane lipid dynamics and width, key determinants of protein function. Methods: Membrane lipid fluidity was measured by fluorescence anisotropy approaches in large unilamellar vesicles (LUVs) of 100 nm diameter containing 1-palmitoyl-2-oleoyl-3-sn-phosphatidylcholine (POPC) and 50 mol% cholesterol with EPA and/or DHA (0-10 mol%). LUVs were treated with the fluorescent probe, 1,6-diphenyl-1,3,5-hexatriene (DPH), at 1 mol% and evaluated using a spectrofluorometer with a polarization accessory. Membrane width ( i.e ., unit cell periodicity) of the samples was determined by small angle x-ray scattering (SAXS). Results: DHA alone increased bulk lipid fluidity as indicated by a dose-dependent reduction in apparent rotational correlation time (ARCT); at 10 mol%, there was a ~20% (p<0.05) reduction from ~19 to ~16 nsec compared to control (untreated membranes). By contrast, EPA had no significant disordering effect except when combined at equimolar levels; the EPA/DHA combination showed a reduction in ARCT to ~18 nsec at 10 mol% that was different from EPA alone (p<0.05). Consistent with these findings, SAXS analysis showed DHA containing membranes had a reduced width compared to EPA by 5% or 3 Å (p<0.05) due to increased trans-gauche isomerizations in the phospholipid acyl chains. Conclusion: EPA maintained membrane fluidity while DHA increased fluidity and thereby reduced membrane width due to its additional carbons and double bond. The EPA/DHA combination increased membrane fluidity compared to control and EPA alone. The disordering effects of DHA may counter EPA stabilizing effects and explain discordant clinical outcomes with different n3-FA formulations.

Effects of Hydrophobic Gold Nanoparticles on Structure and Fluidity of SOPC Lipid Membranes.

Gold nanoparticles (AuNPs) are promising candidates in various biomedical applications such as sensors, imaging, and cancer therapy. Understanding the influence of AuNPs on lipid membranes is important to assure their safety in the biological environment and to improve their scope in nanomedicine. In this regard, the present study aimed to analyze the effects of different concentrations (0.5, 1, and 2 wt.%) of dodecanethiol functionalized hydrophobic AuNPs on the structure and fluidity of zwitterionic 1-stearoyl-2-oleoyl-sn-glycerol-3-phosphocholine (SOPC) lipid bilayer membranes using Fourier-transform infrared (FTIR) spectroscopy and fluorescent spectroscopy. The size of AuNPs was found to be 2.2 ± 1.1 nm using transmission electron microscopy. FTIR results have shown that the AuNPs induced a slight shift in methylene stretching bands, while the band positions of carbonyl and phosphate group stretching were unaffected. Temperature-dependent fluorescent anisotropy measurements showed that the incorporation of AuNPs up to 2 wt.% did not affect the lipid order in membranes. Overall, these results indicate that the hydrophobic AuNPs in the studied concentration did not cause any significant alterations in the structure and membrane fluidity, which suggests the suitability of these particles to form liposome-AuNP hybrids for diverse biomedical applications including drug delivery and therapy.

Micelles-in-Liposome Systems Obtained by Proliposomal Approach for Cannabidiol Delivery: Structural Features and Skin Penetration.

Deformable liposomes represent valuable drug carriers for cutaneous administration. Nevertheless, the fluid lipid membrane can favor the drug leakage during storage. Proliposomes may represent a suitable strategy to solve this issue. As an alternative, a novel carrier, which encloses hydrophobic drugs in the inner core of vesicles, namely, a drug-in-micelles-in-liposome system (DiMiL), has been proposed. In this work, we investigated the possible advantages of combining these two approaches to obtain a formulation able to enhance the skin penetration of cannabidiol (CBD). Proliposomes were prepared by spray-drying or slurry method testing lactose, sucrose, and trehalose as carriers at different sugar/lipid weight ratios. The ratio between soy-phosphatidylcholine (main lipid) and Tween 80 was instead fixed at 85:15 w/w. DiMiL systems were extemporaneously obtained by the hydration of proliposomes with a Kolliphor HS 15 micellar dispersion (containing CBD, when appropriate). Based on the technological properties, sucrose and trehalose at 2:1 sugar/lipid ratio resulted in the best carriers for spray-dried and "slurried" proliposomes, respectively. Cryo-EM images clearly showed the presence of micelles in the aqueous core of lipid vesicles and the presence of sugars did not alter the structural organization of DiMiL systems, as demonstrated by SAXS analyses. All formulations were highly deformable and able to control CBD release regardless of the presence of sugar. The permeation through human epidermis of CBD carried by DiMiL systems was significantly improved compared to that obtained loading the drug in conventional deformable liposomes with the same lipid composition or in an oil solution. Furthermore, the presence of trehalose led to a further slight increase of the flux. Altogether, these results demonstrated that proliposomes may be a valuable intermediate for the preparation of deformable liposome-based cutaneous dosage forms, improving the stability without compromising the overall performances.

Relationship between obesity, insulin resistance and cell membrane properties

Introduction and aim. The obesity is one of the greatest public health problems in developing countries and it is a triggering factor for diabetes associated with insulin resistance. The importance of cell membrane lipids as essential regulators of insulin resistance, since changes in the dynamic properties of the cell membrane (e.g., membrane fluidity), could be one of the events by which obesity affects insulin sensitivity. Thus, the insulin resistance may not only be a cause but also a consequence of lipid disorders such as dyslipidemia and/or cell membrane phospholipid composition change. The modification of plasma membrane lipid composition can change membrane biophysical properties and thus influencing protein-lipid interactions, enzymatic activity and regulation of surface receptors. Alterations in the lipid composition modify the fluidity of plasma membranes and the expression of membrane functions, such as receptor binding and enzyme activities. This review summarizes the current knowledge on the effects of the modulation of plasma membrane lipid composition and membrane fluidity in the functionality of membrane proteins involved in insulin activity, including the insulin receptor, glucose transport and Na + /K + ATPase and, in turn, the key features of the metabolic syndrome. Material and methods. References for that article were found through PubMed and Google Scholar, using terms: “obesity”, “insulin resistance” and “membrane properties”. The research was limited to abstracts and available full-text articles. Analysis of the literature. There is a strong relationship between dietary lipids, membrane lipid profiles and insulin resistance. The changes in the dynamic properties of the cell membrane (e.g., membrane fluidity), could be one of the events by which obesity affects insulin sensitivity. The modification of plasma membrane lipid composition can change membrane biophysical properties and thus influencing protein–lipid interactions, enzymatic activity, and regulation of surface receptors. Modifications of membrane phospholipid composition could have a role in the insulin action by altering membrane fluidity and, as a consequence, the insulin signaling pathway. Conclusion. As conclusion the membrane-lipid therapy approach can be used to treat important pathologies such as obesity and many others diseases such as : cancer, cardiovascular pathologies, neurodegenerative processes, obesity, metabolic disorders, inflammation, and infectious and autoimmune diseases. This pharmacological strategy aims to regulate cell functions by influencing lipid organization and membrane fluidity, inducing a concomitant modulation of membrane protein localization and activity which might serve to reverse the pathological state. Through this review we suggest an in-depth analysis of the membrane lipid therapy field, especially its molecular bases and its relevance to the development of innovative therapeutic approaches.

Phthalates Promote Dissemination of Antibiotic Resistance Genes: An Overlooked Environmental Risk.

Plastics-microorganism interactions have aroused growing environmental and ecological concerns. However, previous studies concentrated mainly on the direct interactions and paid little attention to the ecotoxicology effects of phthalates (PAEs), a common plastic additive that is continuously released and accumulates in the environment. Here, we provide insights into the impacts of PAEs on the dissemination of antibiotic resistance genes (ARGs) among environmental microorganisms. Dimethyl phthalate (DMP, a model PAE) at environmentally relevant concentrations (2-50 μg/L) significantly boosted the plasmid-mediated conjugation transfer of ARGs among intrageneric, intergeneric, and wastewater microbiota by up to 3.82, 4.96, and 4.77 times, respectively. The experimental and molecular dynamics simulation results unveil a strong interaction between the DMP molecules and phosphatidylcholine bilayer of the cell membrane, which lowers the membrane lipid fluidity and increases the membrane permeability to favor transfer of ARGs. In addition, the increased reactive oxygen species generation and conjugation-associated gene overexpression under DMP stress also contribute to the increased gene transfer. This study provides fundamental knowledge of the PAE-bacteria interactions to broaden our understanding of the environmental and ecological risks of plastics, especially in niches with colonized microbes, and to guide the control of ARG environmental spreading.

Cholesterol and melatonin regulated membrane fluidity does not affect the membrane breakage triggered by amyloid-beta peptide

We have studied by means of small angle neutron scattering and diffraction, and molecular dynamics simulations the effect of lipid membrane fluidity on the amyloid-beta peptide interactions with the membrane. These interactions have been discovered previously to trigger the reorganization of model membranes between unilamellar vesicles and planar membranes (bicelle-like structures) during the lipid phase transition. The morphology changes were taking place in rigid membranes prepared of fully saturated lipids and were proposed to play a role in the onset of amyloid related disorders. We show in this study that the replacement of fully saturated lipids by more fluid mono-unsaturated lipids eliminates the mentioned morphology changes, most likely due to the absence of phase transition within the temperature range investigated. We have therefore controlled the membrane rigidity also while ensuring the presence of membrane phase transition within the biologically relevant temperatures. It was done by the addition of melatonin and/or cholesterol to the initial membranes made of saturated lipids. Small angle neutron scattering experiments performed over a range of cholesterol and melatonin concentrations show their distinctive effects on the local membrane structure only. The cholesterol for example affects the membrane curvature such that spontaneously formed unilamellar vesicles are of much larger sizes than those formed by the neat lipid membranes or membranes with melatonin added. The temperature dependent experiments, however, reveal no influence on the previously discovered membrane breakage whether cholesterol or melatonin have been added.

Molecular Rearrangements in Protomembrane Models Probed by Laurdan Fluorescence.

Lipid membranes are a key component of living systems and have been essential to the origin of life. One hypothesis for the origin of life assumes the existence of protomembranes with ancient lipids formed by Fischer-Tropsch synthesis. We determined the mesophase structure and fluidity of a prototypical decanoic (capric) acid-based system, a fatty acid with a chain length of 10 carbons, and a lipid system consisting of a 1:1 mixture of capric acid with a fatty alcohol of equal chain length (C10 mix). To shed light on the mesophase behavior and fluidity of these prebiotic model membranes, we employed Laurdan fluorescence spectroscopy, which reports on the lipid packing and fluidity of membranes, supplemented by small-angle neutron diffraction data. The data are compared with data of the corresponding phospholipid bilayer systems of the same chain length, 1,2-didecanoyl-sn-glycero-3-phosphocholine (DLPC). We demonstrate that the prebiotic model membranes capric acid and the C10 mix show formation of stable vesicular structures needed for cellular compartmentalization at low temperatures only, typically below 20 °C. They reveal the fluid-like lipid dynamic properties needed for optimal physiological function. High temperatures lead to the destabilization of the lipid vesicles and the formation of micellar structures.

A Biophysical Research on the Determination of Morphological and Structural Properties of Coumarin-Loaded Liposomes

The major goal of this research was to examine how coumarin affects lipid model membranes. For this reason, liposome membranes were formed using dimyristoyl phosphatidylcholine (DMPC) as zwitterionic lipid. The influence of coumarin on the morphology, packing order, fluidity, and hydration state of lipid membranes was specifically investigated by means of microscopic (field emission scanning electron microscopy (FE-SEM)) and spectroscopic (attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy) techniques. Taken into account the results obtained with FE-SEM images and analysis, liposomes without and with coumarin have uniform structures and spherical shapes in appearance. However, coumarin-loaded liposomes are observed with an increase in size when compared to a mean diameter of unloaded-liposomes. Considering ATR-FTIR analysis, the investigation of the vibrational bands which belong to the hydrophobic and hydrophilic parts of DMPC lipid reveals that coumarin alters the physical features of the DMPC liposomes by decreasing the order and increasing the fluidity of the system and making hydrogen bonding with the interfacial and headgroup regions of zwitterionic lipid DMPC. Finally, performing more biophysical studies on the interactions of biologically active compounds with model membranes plays an important role in determining the molecular action mechanisms of these compounds in drug discovery and formulations.