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Highly concentrated lens proteins, mostly β- and γ-crystallin, are responsible for maintaining the structure and refractivity of the eye lens. However, with aging and cataract formation, β- and γ-crystallin are associated with the lens membrane or other lens proteins forming high-molecular-weight proteins, which further associate with the lens membrane, leading to light scattering and cataract development. The mechanism by which β- and γ-crystallin are associated with the lens membrane is unknown. This work aims to study the interaction of β- and γ-crystallin with the phospholipid membrane with and without cholesterol (Chol) with the overall goal of understanding the role of phospholipid and Chol in β- and γ-crystallin association with the membrane. Small unilamellar vesicles made of Chol/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (Chol/POPC) membranes with varying Chol content were prepared using the rapid solvent exchange method followed by probe tip sonication and then dispensed on freshly cleaved mica disk to prepare a supported lipid membrane. The βL- and γ-crystallin from the cortex of the bovine lens was used to investigate the time-dependent association of βL- and γ-crystallin with the membrane by obtaining the topographical images using atomic force microscopy. Our study showed that βL-crystallin formed semi-transmembrane defects, whereas γ-crystallin formed transmembrane defects on the phospholipid membrane. The size of semi-transmembrane defects increases significantly with incubation time when βL-crystallin interacts with the membrane. In contrast, no significant increase in transmembrane defect size was observed in the case of γ-crystallin. Our result shows that Chol inhibits the formation of membrane defects when βL- and γ-crystallin interact with the Chol/POPC membrane, where the degree of inhibition depends upon the amount of Chol content in the membrane. At a Chol/POPC mixing ratio of 0.3, membrane defects were observed when both βL- and γ-crystallin interacted with the membrane. However, at a Chol/POPC mixing ratio of 1, no association of γ-crystallin with the membrane was observed, which resulted in a defect-free membrane, and the severity of the membrane defect was decreased when βL-crystallin interacted with the membrane. The semi-transmembrane or transmembrane defects formed by the interaction of βL- and γ-crystallin on phospholipid membrane might be responsible for light scattering and cataract formation. However, Chol suppressed the formation of such defects in the membrane, likely maintaining lens membrane homeostasis and protecting against cataract formation. [ABSTRACT FROM AUTHOR]

Morphological features of the nanoform of a phospholipid composition (NFPh), which can be used as an individual pharmaceutic agent or as a platform for designing drug delivery systems, have been studied using atomic force microscopy (AFM). NFPh has been developed, and its characteristics have been investigated using conventional drug analysis methods, including the determination of the mean diameter of nanosized vesicles in the emulsion via dynamic light scattering (DLS). Using DLS, the mean diameter of the vesicles was found to be ~20 nm. AFM imaging of the surface has revealed four types of objects related to NFPh: (1) compact objects; (2) layer fragments; (3) lamellar structures; and (4) combined objects containing the compact and extended parts. For type (4) objects, it has been found that the geometric ratio of the volume of the convex part to the total area of the entire object is constant. It has been proposed that these objects formed owing to fusion of vesicles of the same size (with the same surface-to-volume ratio). It has been shown that this is possible for vesicles with diameters of 20 nm. This diameter is in good coincidence with the value obtained using DLS. [ABSTRACT FROM AUTHOR]

The interaction between macromolecular chains and phospholipid membranes in aqueous solution was investigated using dissipative particle dynamics simulations. Two cases were considered, one in which the macromolecular chains were pulled along parallel to the membrane surfaces and another in which they were pulled vertical to the membrane surfaces. Several parameters, including the radius of gyration, shape factor, particle number, and order parameter, were used to investigate the interaction mechanisms during the dynamics processes by adjusting the pulling force strength of the chains. In both cases, the results showed that the macromolecular chains undergo conformational transitions from a coiled to a rod-like structure. Furthermore, the simulations revealed that the membranes can be damaged and repaired during the dynamic processes. The role of the pulling forces and the adsorption interactions between the chains and membranes differed in the parallel and perpendicular pulling cases. These findings contribute to our understanding of the interaction mechanisms between macromolecules and membranes, and they may have potential applications in biology and medicine. [ABSTRACT FROM AUTHOR]

Oxidative stress and metal dyshomeostasis are considered crucial factors in the pathogenesis of Alzheimer's disease (AD). Indeed, transition metal ions such as Cu(II) can generate reactive oxygen species (ROS) via O2 Fenton-like reduction, catalyzed by Cu(II) coordinated to the amyloid-beta (Aβ) peptide. Despite intensive efforts, the mechanisms of ROS-induced molecular damage remain poorly understood. In the present paper, we investigate, on the basis of Density Functional Theory (DFT) computations, a possible mechanism of the OH radical propagation toward membrane phospholipid polar head and fatty acid chains starting from the end-product of the OH radical generation by Cu(II)-Aβ. Using phosphatidylcholine as a model of a single unit inside a membrane, we evaluated the thermochemistry of the OH propagation with the oxidation of a C-H bond and the formation of the radical moiety. The DFT results show that Cu(II)-Aβ-OH can oxidize only sn-2 C-H bonds of the polar head and can easily oxidize the C-H bond adjacent to the carbon–carbon double bond in a mono or bis unsaturated fatty acid chain. These results are discussed on the basis of the recent literature on in vitro Aβ metal-catalyzed oxidation and on the possible implications in the AD oxidative stress mechanism. [ABSTRACT FROM AUTHOR]

Membrane-disrupting lactylates are an important class of surfactant molecules that are esterified adducts of fatty acid and lactic acid and possess industrially attractive properties, such as high antimicrobial potency and hydrophilicity. Compared with antimicrobial lipids such as free fatty acids and monoglycerides, the membrane-disruptive properties of lactylates have been scarcely investigated from a biophysical perspective, and addressing this gap is important to build a molecular-level understanding of how lactylates work. Herein, using the quartz crystal microbalance–dissipation (QCM-D) and electrochemical impedance spectroscopy (EIS) techniques, we investigated the real-time, membrane-disruptive interactions between sodium lauroyl lactylate (SLL)—a promising lactylate with a 12-carbon-long, saturated hydrocarbon chain—and supported lipid bilayer (SLB) and tethered bilayer lipid membrane (tBLM) platforms. For comparison, hydrolytic products of SLL that may be generated in biological environments, i.e., lauric acid (LA) and lactic acid (LacA), were also tested individually and as a mixture, along with a structurally related surfactant (sodium dodecyl sulfate, SDS). While SLL, LA, and SDS all had equivalent chain properties and critical micelle concentration (CMC) values, our findings reveal that SLL exhibits distinct membrane-disruptive properties that lie in between the rapid, complete solubilizing activity of SDS and the more modest disruptive properties of LA. Interestingly, the hydrolytic products of SLL, i.e., the LA + LacA mixture, induced a greater degree of transient, reversible membrane morphological changes but ultimately less permanent membrane disruption than SLL. These molecular-level insights support that careful tuning of antimicrobial lipid headgroup properties can modulate the spectrum of membrane-disruptive interactions, offering a pathway to design surfactants with tailored biodegradation profiles and reinforcing that SLL has attractive biophysical merits as a membrane-disrupting antimicrobial drug candidate. [ABSTRACT FROM AUTHOR]

It has been confirmed that skeletal muscle cells have the capability to receive foreign plasmid DNA (pDNA) and express functional proteins. This provides a promisingly applicable strategy for safe, convenient, and economical gene therapy. However, intramuscular pDNA delivery efficiency was not high enough for most therapeutic purposes. Some non-viral biomaterials, especially several amphiphilic triblock copolymers, have been shown to significantly improve intramuscular gene delivery efficiency, but the detailed process and mechanism are still not well understood. In this study, the molecular dynamics simulation method was applied to investigate the structure and energy changes of the material molecules, the cell membrane, and the DNA molecules at the atomic and molecular levels. From the results, the interaction process and mechanism of the material molecules with the cell membrane were revealed, and more importantly, the simulation results almost completely matched the previous experimental results. This study may help us design and optimize better intramuscular gene delivery materials for clinical applications. [ABSTRACT FROM AUTHOR]

The molecular interaction of black tea components with phospholipid vesicles has been investigated to elucidate the various functions of black tea infusions, such as astringency, inhibition of cholesterol absorption, and inactivation of viruses. We have developed a simple method to analyze the turbidity of phospholipid vesicle solutions reacted with black tea infusions or components as an indicator of the molecular interaction. Using a portable visible spectrophotometer, the dose-dependency of catechins, theaflavins, thearubigins, and black tea infusions on turbidity was analyzed. The results indicate that authentic catechins and theaflavins independently caused aggregation of the phospholipid vesicles; however, their concentrations in the tea infusions were insufficient. Meanwhile, thearubigins prepared from black tea leaves caused aggregation at the concentration found in the tea infusions. It is concluded that thearubigins, instead of theaflavins, mainly contribute to the interaction with phospholipid vesicles. [ABSTRACT FROM AUTHOR]

The phospholipid membrane-water partition coefficients ( K MW ) and equilibrium binding affinities for human serum albumin (HSA) of 60 structurally diverse perfluoroalkyl and polyfluoroalkyl substances (PFAS) were evaluated through laboratory measurements and modeling to enhance our understanding of PFAS distribution in organisms. Per- and polyfluoroalkyl carboxylic acids exhibited a 0.36 ± 0.01 log-unit increase in K MW as the fluorinated carbon chain length increased from C 4 to C 16 , while per- and polyfluoroalkyl sulfonates showed a 0.37 ± 0.02 log-unit increase. The highest HSA affinity range was observed between C 6 and C 10 , with the following structural subclass order: per- and polyfluoroalkyl sulfonates ≈ ether sulfonic acids > polyfluoroalkyl carboxylic acids > fluorotelomer unsaturated carboxylic acids > phosphate diesters ≈ per- and polyfluoroether carboxylic acids. A comparison between association rate constants (K A . Based on in vitro results, exposure-dependent PFAS partitioning in organisms was modeled by comparing distribution coefficients between PFAS in phospholipid membranes and HSA at different PFAS concentrations and demonstrated that at lower concentrations, PFAS had higher partitioning in HSA, while with increasing concentration, the proportion of binding relative to the aqueous phase shifted toward the phospholipid membrane. Few studies have compared the bioaccumulation of PFAS in phospholipid membranes and HSA. This research reports that protein-water distribution coefficients are higher than membrane-water partitioning coefficients at lower PFAS concentrations, which may have implications for interpreting exposure data and toxicity experiments.4 to C 10 . Based on in vitro results, exposure-dependent PFAS partitioning in organisms was modeled by comparing distribution coefficients between PFAS in phospholipid membranes and HSA at different PFAS concentrations and demonstrated that at lower concentrations, PFAS had higher partitioning in HSA, while with increasing concentration, the proportion of binding relative to the aqueous phase shifted toward the phospholipid membrane. Few studies have compared the bioaccumulation of PFAS in phospholipid membranes and HSA. This research reports that protein-water distribution coefficients are higher than membrane-water partitioning coefficients at lower PFAS concentrations, which may have implications for interpreting exposure data and toxicity experiments.

Aims: To investigate the antibacterial effects of tea theaflavins and catechins against Bacillus coagulans and the underlying mechanism of antibacterial action. Methods and Results: Bactericidal activities of theaflavin and its analogues were evaluated and compared with that of epigallocatechin gallate. Theaflavin derivatives exhibited high bactericidal activity at 50 μmol L−1, whereas epigallocatechin gallate did not, even at 500 μmol L−1. Furthermore, we investigated the adsorption of theaflavins to model phospholipid membranes and corresponding effects on membrane fluidity to reveal their effects on the B. coagulans cell surface. Cell membrane fluidity was decreased after treatment with theaflavin derivatives with one or more galloyl moieties. Quartz‐crystal microbalance analysis showed a strong affinity of the membrane phosphatidyl glycerol (PG) bilayers for theaflavin derivatives, correlating their bactericidal activity. Conclusion: These findings suggest that theaflavins could effectively inhibit B. coagulans by decreasing cell membrane fluidity. Significance and Impact: Bacillus coagulans is a spore‐forming heat‐resistant bacterium responsible for spoilage in low‐acidic beverages. Natural antimicrobial components in tea‐based beverages are central to reducing microbial contamination and product quality deterioration, although mechanisms underlying their antimicrobial action remain obscure. This study highlights the inhibitory action of theaflavins on B. coagulans and their potential application in food and beverage industries. [ABSTRACT FROM AUTHOR]

Titanium dioxide (TiO2), as a representative of metallic oxides, is widely used as food additive to serve as coloring or antibacterial packaging fortifier. However, in recent years, the potential hazards of nano-sized TiO2 food additives to human beings is still in doubt. In this work, we systematically studied the interactions between three sizes of TiO2 particles and the cell membrane systems with confocal laser scanning microscopy. We used both giant unilamellar vesicles and human colon cancer cells to mimic actual cell membrane systems. The results demonstrate the strong effect of particle size on membrane disruption and leakage behaviors. Among the three sizes of TiO2 nanoparticles (NPs) used in this work, the TiO2 NPs with the size of 110-300 nm are safe. In contrast, NPs with the size of 10-30 nm and 50-100 nm will cause the rupture and leakage of cell membranes. These indicates that the cytotoxicity of nano-sized TiO2 particles increases with the decrease of particle sizes. In addition, it is found that the size effect of TiO2 particles further depends on the membrane charge state. Simulations were also introduced to understand the results. This study would provide a theoretical basis for the production designing and safety standard of metallic oxide food additives. [ABSTRACT FROM AUTHOR]

It has been confirmed that skeletal muscle cells have the capability to receive foreign plasmid DNA (pDNA) and express functional proteins. This provides a promisingly applicable strategy for safe, convenient, and economical gene therapy. However, intramuscular pDNA delivery efficiency was not high enough for most therapeutic purposes. Some non-viral biomaterials, especially several amphiphilic triblock copolymers, have been shown to significantly improve intramuscular gene delivery efficiency, but the detailed process and mechanism are still not well understood. In this study, the molecular dynamics simulation method was applied to investigate the structure and energy changes of the material molecules, the cell membrane, and the DNA molecules at the atomic and molecular levels. From the results, the interaction process and mechanism of the material molecules with the cell membrane were revealed, and more importantly, the simulation results almost completely matched the previous experimental results. This study may help us design and optimize better intramuscular gene delivery materials for clinical applications.

Previous studies from our lab have shown that the antimicrobial peptide F1 obtained from the milk fermentation by Lactobacillus paracasei FX-6 derived from Tibetan kefir was different from common antimicrobial peptides; specifically, F1 simultaneously inhibited the growth of Gram-negative and Gram-positive bacteria. Here, we present follow-on work demonstrating that after the antimicrobial peptide F1 acts on either Escherichia coli ATCC 25922 (E. coli) or Staphylococcus aureus ATCC 63589 (S. aureus), their respective bacterial membranes were severely deformed. This deformation allowed leakage of potassium and magnesium ions from the bacterial membrane. The interaction between the antimicrobial peptide F1 and the bacterial membrane was further explored by artificially simulating the bacterial phospholipid membranes and then extracting them. The study results indicated that after the antimicrobial peptide F1 interacted with the bacterial membranes caused significant calcein leakage that had been simulated by different liposomes. Furthermore, transmission electron microscopy observations revealed that the phospholipid membrane structure was destroyed and the liposomes presented aggregation and precipitation. Quartz Crystal Microbalance with Dissipation (QCM-D) results showed that the antimicrobial peptide F1 significantly reduced the quality of liposome membrane and increased their viscoelasticity. Based on the study's findings, the phospholipid membrane particle size was significantly increased, indicating that the antimicrobial peptide F1 had a direct effect on the phospholipid membrane. Conclusively, the antimicrobial peptide F1 destroyed the membrane structure of both Gram-negative and Gram-positive bacteria by destroying the shared components of their respective phospholipid membranes which resulted in leakage of cell contents and subsequently cell death.

Abstract Background After the discovery of membrane-reversible electroporation decades ago, the procedure has been used extensively in biology, biotechnology and medicine. The research on the basic mechanism has increasingly attracted attention. Although most research has focused on models that consider all atomic and molecular interactions and much atomic-level information can be obtained, the huge computational demand limits the models to simulations of only a few nanometers on the spatial scale and a few nanoseconds on the time scale. In order to more comprehensively study the reversible electroporation mechanism of phospholipid membrane on the nanoscale and at longer time intervals of up to 100 ns, we developed a dipalmitoylphosphatidylcholine (DPPC) phospholipid membrane model with the coarse-grained Martini force field. The model was tested by separately examining the morphology of the phospholipid membrane, the hydrophilic channel size, the distribution of the voltage potential on both sides of the membrane, and the movement of water molecules and ions during electroporation. Results The results showed that the process went through several stages: (1) the formation of the pore with defects originating on the surface. (2) The maintenance of the pore. The defects expanded to large pores and the size remains unchanged for several nanoseconds. (3) Pore healing stage due to self-assembly. Phospholipid membrane shrunk and the pore size decreased until completely closed. The pores were not circular in cross-section for most of the time and the potential difference across the membrane decreased dramatically after the pores formed, with almost no restoration of membrane integrity even when the pores started to close. Conclusions The mechanism of the reversible electroporation process on the nanoscale level, including defects, expansion, stability, and pore closing stages on a longer time scale of up to 100 ns was demonstrated more comprehensively with the coarse-grained Martini force field, which took both the necessary molecular information and the calculation efficiency into account.

Purpose/Aim: The amount of membrane-bound α-crystallin increases significantly with age and cataract formation, accompanied by a corresponding decline in the level of α-crystallin in the lens cytoplasm. The purpose of this research is to evaluate the binding affinity of α-crystallin to the phospholipid membranes as well as the physical properties of the membranes after α-crystallin binding. Materials and Methods: The continuous wave and saturation recovery electron paramagnetic resonance (EPR) methods were used to obtain the information about the binding affinity and the physical properties of the membrane. In this approach, the cholesterol analog spin label CSL was incorporated in the membrane and the binding of α-crystallin to the membrane was monitored by this spin label. Small uni-lamellar vesicles were prepared from 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) with 1% of CSL. The measured membrane properties included the mobility parameter, fluidity, and the oxygen transport parameter. Results: The binding affinity (Ka) of α-crystallin with the POPC membrane was estimated to be 4.9 ± 2.4 µM−1. The profiles of mobility parameter showed that mobility parameter decreased with an increase in the binding of α-crystallin. The profiles of spin-lattice relaxation rate showed that the spin-lattice relaxation rate decreased with an increase in binding. These results show that the binding of α-crystallin makes the membrane more immobilized near the head group region of the phospholipids. Furthermore, the profiles of the oxygen transport parameter indicated that the oxygen transport parameter decreased with an increase of binding, indicating the binding of α-crystallin forms a barrier for the passage of non-polar molecules which supports the barrier hypothesis. Conclusions: The binding of α-crystallin to the membrane alters the physical properties of the membranes, and this plays a significant role in modulating the integrity of the membranes. EPR techniques are useful in studying α-crystallin membrane interactions. [ABSTRACT FROM AUTHOR]

The use of drugs derived from benzothiadiazine, a bicyclic heterocyclic benzene derivative, has become a widespread treatment for diseases such as hypertension, low blood sugar or the human immunodeficiency virus, among others. In this work we have investigated the interactions of benzothiadiazine and four of its derivatives designed in silico with model zwitterionic cell membranes formed by dioleoylphosphatidylcholine, 1,2-dioleoyl-sn-glycero-3-phosphoserine and cholesterol at the liquid–crystal phase inside aqueous potassium chloride solution. We have elucidated the local structure of benzothiadiazine by means of microsecond molecular dynamics simulations of systems including a benzothiadiazine molecule or one of its derivatives. Such derivatives were obtained by the substitution of a single hydrogen site of benzothiadiazine by two different classes of chemical groups, one of them electron-donating groups (methyl and ethyl) and another one by electron-accepting groups (fluorine and trifluoromethyl). Our data have revealed that benzothiadiazine derivatives have a strong affinity to stay at the cell membrane interface although their solvation characteristics can vary significantly—they can be fully solvated by water in short periods of time or continuously attached to specific lipid sites during intervals of 10–70 ns. Furthermore, benzothiadiazines are able to bind lipids and cholesterol chains by means of single and double hydrogen-bonds of characteristic lengths between 1.6 and 2.1 Å.

Nanocarriers are used globally in diverse fields to encapsulate drug toovercome various problems associated with different drug delivery systems such asstability, solubility, improvement in functional activities, homogeneity, and protection from physical and chemical hazard destructions. In the field of biomedicine, this approachis considered to be of particular importance as it can easily overcome the issues related to biocompatibility, bioavailability, toxicity profile, and therapeutic side effects. Lipid-based delivery systems have evolved as a newer approach in drug delivery. Advancement, development, and design modification of the lipid-based drug delivery systems have given rise to hybrid structures containing both inorganic and organic parts called cerasomes. Cerasomes are a modified form of liposomes that can overcome the limitations related to lipid nanoparticles. However, these cerasomes are also effective in treating diabetes mellitus, which is a metabolic disorder that has affecteda vast population worldwide for the last few decades. The development of cerasomes for the treatment of diabetes has provided a new window for researchers to overcome the different problems connected to the current therapies. This article provides a thorough assessment of the hybrid liposomal cerasomes literature and how it can be effectively employed in the treatment of diabetes.

The magneto-mechanical actuation (MMA) of magnetic nanoparticles with a low-frequency alternating magnetic field (AMF) can be used to destroy cancer cells. So far, MMA was tested on different cells using different nanoparticles and different field characteristics, which makes comparisons and any generalizations about the results of MMA difficult. In this paper we propose the use of giant unilamellar vesicles (GUVs) as a simple model system to study the effect of MMA on a closed lipid bilayer membrane, i.e., a basic building block of any cell. The GUVs were exposed to barium-hexaferrite nanoplatelets (NPLs, ~50 nm wide and 3 nm thick) with unique magnetic properties dominated by a permanent magnetic moment that is perpendicular to the platelet, at different concentrations (1–50 µg/mL) and pH values (4.2–7.4) of the aqueous suspension. The GUVs were observed with an optical microscope while being exposed to a uniaxial AMF (3–100 Hz, 2.2–10.6 mT). When the NPLs were electrostatically attached to the GUV membranes, the MMA induced cyclic fluctuations of the GUVs' shape corresponding to the AMF frequency at the low NPL concentration (1 µm/mL), whereas the GUVs were bursting at the higher concentration (10 µg/mL). Theoretical considerations suggested that the bursting of the GUVs is a consequence of the local action of an assembly of several NPLs, rather than a collective effect of all the absorbed NPLs. [ABSTRACT FROM AUTHOR]

The elastic and viscous properties of biological membranes play a vital role in controlling cell functions that require local reorganization of the membrane components as well as dramatic shape changes such as endocytosis, vesicular trafficking, and cell division. These properties are widely acknowledged to depend on the unique composition of lipids within the membrane, yet the effects of lipid mixing on the membrane biophysical properties remain poorly understood. Here, we present a comprehensive characterization of the structural, elastic, and viscous properties of fluid membranes composed of binarymixtures of lipids with different tail lengths. We show that the mixed lipid membrane properties are not simply additive quantities of the single-component analogs. Instead, the mixed membranes are more dynamic than either of their constituents, quantified as a decrease in their bending modulus, area compressibility modulus, and viscosity. While the enhanced dynamics are seemingly unexpected, we show that the measured moduli and viscosity for both the mixed and single-component bilayers all scale with the area per lipid and collapse onto respective master curves. This scaling links the increase in dynamics to mixing induced changes in the lipid packing and membrane structure. More importantly, the results show that the membrane properties can be manipulated through lipid composition the same way bimodal blends of surfactants, liquid crystals, and polymers are used to engineer the mechanical properties of soft materials, with broad implications for understanding how lipid diversity relates to biomembrane function. [ABSTRACT FROM AUTHOR]

Multinanoparticles interacting with the phospholipid membranes in solution were studied by dissipative particle dynamics simulation. The selected nanoparticles have spherical or cylindrical shapes, and they have various initial velocities in the dynamical processes. Several translocation modes are defined according to their characteristics in the dynamical processes, in which the phase diagrams are constructed based on the interaction strengths between the particles and membranes and the initial velocities of particles. Furthermore, several parameters, such as the system energy and radius of gyration, are investigated in the dynamical processes for the various translocation modes. Results elucidate the effects of multiparticles interacting with the membranes in the biological processes. [ABSTRACT FROM AUTHOR]

Background: After the discovery of membrane-reversible electroporation decades ago, the procedure has been used extensively in biology, biotechnology and medicine. The research on the basic mechanism has increasingly attracted attention. Although most research has focused on models that consider all atomic and molecular interactions and much atomic-level information can be obtained, the huge computational demand limits the models to simulations of only a few nanometers on the spatial scale and a few nanoseconds on the time scale. In order to more comprehensively study the reversible electroporation mechanism of phospholipid membrane on the nanoscale and at longer time intervals of up to 100 ns, we developed a dipalmitoylphosphatidylcholine (DPPC) phospholipid membrane model with the coarse-grained Martini force field. The model was tested by separately examining the morphology of the phospholipid membrane, the hydrophilic channel size, the distribution of the voltage potential on both sides of the membrane, and the movement of water molecules and ions during electroporation.Results: The results showed that the process went through several stages: (1) the formation of the pore with defects originating on the surface. (2) The maintenance of the pore. The defects expanded to large pores and the size remains unchanged for several nanoseconds. (3) Pore healing stage due to self-assembly. Phospholipid membrane shrunk and the pore size decreased until completely closed. The pores were not circular in cross-section for most of the time and the potential difference across the membrane decreased dramatically after the pores formed, with almost no restoration of membrane integrity even when the pores started to close.Conclusions: The mechanism of the reversible electroporation process on the nanoscale level, including defects, expansion, stability, and pore closing stages on a longer time scale of up to 100 ns was demonstrated more comprehensively with the coarse-grained Martini force field, which took both the necessary molecular information and the calculation efficiency into account. [ABSTRACT FROM AUTHOR]

The amyloid-β (Aβ) peptides are key molecules in Alzheimer's disease (AD) pathology. They interact with cellular membranes, and can bind metal ions outside the membrane. Certain oligomeric Aβ aggregates are known to induce membrane perturbations and the structure of these oligomers—and their membrane-perturbing effects—can be modulated by metal ion binding. If the bound metal ions are redox active, as e.g., Cu and Fe ions are, they will generate harmful reactive oxygen species (ROS) just outside the membrane surface. Thus, the membrane damage incurred by toxic Aβ oligomers is likely aggravated when redox-active metal ions are present. The combined interactions between Aβ oligomers, metal ions, and biomembranes may be responsible for at least some of the neuronal death in AD patients. [ABSTRACT FROM AUTHOR]

The molecular interaction between common polymer chains and the cell membrane is unknown. Molecular dynamics simulations offer an emerging tool to characterise the nature of the interaction between common degradable polymer chains used in biomedical applications, such as polycaprolactone, and model cell membranes. Herein we characterise with all-atomistic and coarse-grained molecular dynamics simulations the interaction between single polycaprolactone chains of varying chain lengths with a phospholipid membrane. We find that the length of the polymer chain greatly affects the nature of interaction with the membrane, as well as the membrane properties. Furthermore, we next utilise advanced sampling techniques in molecular dynamics to characterise the two-dimensional free energy surface for the interaction of varying polymer chain lengths (short, intermediate, and long) with model cell membranes. We find that the free energy minimum shifts from the membrane-water interface to the hydrophobic core of the phospholipid membrane as a function of chain length. Finally, we perform coarse-grained molecular dynamics simulations of slightly larger membranes with polymers of the same length and characterise the results as compared with all-atomistic molecular dynamics simulations. These results can be used to design polymer chain lengths and chemistries to optimise their interaction with cell membranes at the molecular level. [ABSTRACT FROM AUTHOR]

The plasma membranes of the human lens fiber cell are overloaded with cholesterol that not only saturates the phospholipid bilayer of these membranes but also leads to the formation of pure cholesterol bilayer domains. Cholesterol level increases with age, and for older persons, it exceeds the cholesterol solubility threshold, leading to the formation of cholesterol crystals. All these changes occur in the normal lens without too much compromise to lens transparency. If the cholesterol content in the cell membranes of other organs increases to extent where cholesterol crystals forma, a pathological condition begins. In arterial cells, minute cholesterol crystals activate inflammasomes, induce inflammation, and cause atherosclerosis development. In this review, we will indicate possible factors that distinguish between beneficial and negative cholesterol action, limiting cholesterol actions to those performed through cholesterol in cell membranes and by cholesterol crystals. [ABSTRACT FROM AUTHOR]

A pyrenylated fluorogenic probe has been designed that can detect heavy metal pollutants exclusively at the bilayer interface. The compound, due to extensive self-aggregation, showed no interaction with metal ions in the bulk solution phase. However, effective, nanomolar level detection of multiple metal ions, such as Cu2+, Hg2+, and Ni2+, etc. was achieved exclusively in vesicular aggregates. The optical response towards metal ions, including selectivity and sensitivity, largely depends on the microenvironment around the probe molecules, governed by the nature of the bilayer membrane (polarity, order, interfacial hydration, etc). In zwitterionic membranes, like DPPC, Hg2+-induced fluorescence quenching was witnessed along with red-shifted emission maxima. On the contrary, turn-off responses along with blue-shifted in maxima were noted upon addition of both Cu2+ and Ni2+ ions in the anionic phospholipid vesicle, DPPA. Moreover, an improvement in sensitivity was witnessed when the probe was embedded into phospholipid vesicles with a fluid-like liquid crystalline phase. The larger mobility of the probe molecules on the bilayer membrane, resulting in ease of reorganization, might be the probable reason for this. [Display omitted] • Multiple metal ion sensing at lipid-water interface. • Microenvironment-Dependent modulation in analytical performance. • Protonation at anionic interface due to acidic local pH. • Fluidity-dependent reorganization of probe molecules on bilayer surface. [ABSTRACT FROM AUTHOR]

The aim of the present study was to develop layered double hydroxide (LDH) nanoparticles coated with PEGylated phospholipid membrane. By comparing the size distribution and zeta potential, the weight ratio of LDH to lipid materials which constitute the outside membrane was identified as 2:1. Transmission electron microscopy photographs confirmed the core-shell structure of PEGylated phospholipid membrane coated LDH (PEG-PLDH) nanoparticles, and cell cytotoxicity assay showed their good cell viability on Hela and BALB/C-3T3 cells over the concentration range from 0.5 to 50 μg/mL.

Abstract The interaction of water with membranes is fundamental in many biological processes. Recently we found that, upon increasing hydration, water molecules first fill completely the interior of the membrane, next accumulate in layers in the exterior region. Here, we show by all-atom simulations that the translational and rotational dynamics of water molecules is strongly determined by their local distance to the membrane so that we can identify the existence of an interface between the first hydration shell, partially made of hydration water bound to the membrane, and the next shells entirely made of unbound hydration water. Bound hydration water has a possible structural role and an extremely slow dynamics, while unbound hydration water, with no water-lipids hydrogen bonds, has a dynamics ten time faster than bound water but still one order of magnitude slower than bulk water. Our results could be relevant to understand the slowdown of biological activity upon dehydration. Highlights • Water near biomembranes separates in bound and unbound hydration water. • Bound: almost frozen in interior and 1st hydration shell, often bridging lipids • Unbound: no bonding with lipids, more mobile than bound, slower than bulk • Sharp dynamic change (interface) at approximately 5 Å away from membrane • At < 5 Å bound water is a large component, at > 5 Å only unbound. [ABSTRACT FROM AUTHOR]

Abstract Casein micelles are ~200 nm electronegative particles that constitute 80 wt% of the milk proteins. During synthesis in the lactating mammary cells, caseins are thought to interact in the form of ~20 nm assemblies, directly with the biological membranes of the endoplasmic reticulum and/or the Golgi apparatus. However, conditions that drive this interaction are not yet known. Atomic force microscopy imaging and force spectroscopy were used to directly observe the adsorption of casein particles on supported phospholipid bilayers with controlled compositions to vary their phase state and surface charge density, as verified by X-ray diffraction and zetametry. At pH 6.7, the casein particles adsorbed onto bilayer phases with zwitterionic and liquid-disordered phospholipid molecules, but not on phases with anionic or ordered phospholipids. Furthermore, the presence of adsorbed caseins altered the stability of the yet exposed bilayer. Considering their respective compositions and symmetry/asymmetry, these results cast light on the possible interactions of casein assemblies with the organelles' membranes of the lactating mammary cells. Graphical abstract Unlabelled Image Highlights • Negatively charged 20-nm casein particles interact with membranes on milk synthesis. • Adsorption of individual casein particles onto lipid bilayers is observed using AFM. • Casein particles do not adsorb onto densely packed phospholipids in ordered phase. • Casein particles do not adsorb onto anionic phospholipids, even in disordered phase. • Casein particles adsorb onto zwitterionic and disordered phospholipid phase. [ABSTRACT FROM AUTHOR]

Graphical abstract Snapshots of DPPC-serotonin (left) and DPPC-tyrosine (right) binding configurations. Highlights • A competition between small-molecule binding to water and to DPPC has been observed, with stable structures including simultaneous binding to both DPPC and water. • Histidine is solvated by water most cases, with very low affinity to the membrane. • Serotonin shows huge affinity for the phospholipid interface, where most stable binding sites are those of glycerol and phosphate oxygens. • All molecules stay at the water-membrane interface, so that crossing the membrane by diffusion is highly uncommon in the time scale of our simulations. Abstract Free energy barriers associated to the binding of small-molecules at phospholipid zwitterionic membranes have been computed at 323 K for a variety of species: tryptophan, histidine, tyrosine, serotonin and melatonin bound to a model membrane formed by di-palmitoyl-phosphatidyl-choline lipids inside aqueous sodium chloride solution. We have computed the radial distribution functions of all species for a variety of membrane and water-related sites and extracted potentials of mean force through the reversible work theorem. In all cases but histidine, the molecular probes are able to either be fully solvated by water or be embedded into the interface of the membrane. Our results indicate that binding of all species to water corresponds to free energy barriers of heights between 0.2 and 1.75 kcal/mol. Free energy barriers of association of small-molecules to lipid chains range between 0.6 and 3.1 kcal/mol and show different characteristics: all species but histidine are most likely bound to oxygens belonging to the phosphate and to the glycerol groups. Histidine shows a clear preference to be fully solvated by water whereas the aqueous solvation of serotonin is the less likely case of them all. No free permeation through the membrane of any small-molecule has been observed during the time span of the simulation experiments. [ABSTRACT FROM AUTHOR]

Abstract Microcosm experiments with the well-studied denitrifier Thaurera aromatica show a link between a higher maximum membrane concentration (MMC) of the toxic organic solvents 1-octanol and 4-chlorophenol and a higher degree of saturation (DoS) of the fatty acids in the cell membrane. This coincides with less pronounced stable isotope fractionation during denitrification. We suggest that the change in cell membrane fluidity and the cell’s stress response leads to a decrease in nitrate transport across the cell membrane and/or an increase in the relative ratio of respiratory nitrate reduction rate versus efflux of unreacted nitrate. Both models show that the apparent kinetic isotope effect (AKIE) approach unity and thus reduce the extent of the resulting stable isotope enrichment factor ε15N-NO 3 − in dissolved nitrate during denitrification, as experimentally and mathematically shown in this study. This may lead to an underestimation of nitrate reduction determined by nitrate stable isotope analysis in aquatic habitats where various types of stresses may affect the physiology of the driving microorganisms. [ABSTRACT FROM AUTHOR]

Free energy surfaces associated to the adsorption of metal cations (, , , and ) in biological environments have been computed by metadynamics simulations. In all cases, the systems were modelled using the CHARMM36 force field. The free-energy landscapes unveil specific binding behaviour of metal cations. So, and are more likely to stay in the aqueous solution, and can easily bind to a few lipid oxygens by overcoming low free-energy barriers. Differently, is most stable when bound to four lipid oxygens of the membranes, rather than being hydrated in the aqueous solution. Finally, is tightly hydrated, and can hardly lose a hydration water and bind directly to the membranes. When cholesterol is included inside the membrane at concentration up to 50%, the resulting free-energy landscapes reveal the competition between binding of sodium to water and to lipid head groups, although the binding competitiveness of lipid head groups is diminished by cholesterol contents. When cholesterol concentration is greater than 30%, the ionic binding is significantly reduced, which coincides with the phase transition point of DMPC-cholesterol membranes from a liquid-disordered phase to a liquid-ordered phase. [ABSTRACT FROM AUTHOR]

The Na + ,K + -ATPase, which is present in the plasma membrane of all animal cells, plays a crucial role in maintaining the Na + and K + electrochemical potential gradients across the membrane. Recent studies have suggested that the N-terminus of the protein's catalytic α-subunit is involved in an electrostatic interaction with the surrounding membrane, which controls the protein's conformational equilibrium. However, because the N-terminus could not yet be resolved in any X-ray crystal structures, little information about this interaction is so far available. In measurements utilising poly- l -lysine as a model of the protein's lysine-rich N-terminus and using lipid vesicles of defined composition, here we have identified the most likely origin of the interaction as one between positively charged lysine residues of the N-terminus and negatively charged headgroups of phospholipids (notably phosphatidylserine) in the surrounding membrane. Furthermore, to isolate which segments of the N-terminus could be involved in membrane binding, we chemically synthesized N-terminal fragments of various lengths. Based on a combination of results from RH421 UV/visible absorbance measurements and solid-state 31 P and 2 H NMR using these N-terminal fragments as well as MD simulations it appears that the membrane interaction arises from lysine residues prior to the conserved LKKE motif of the N-terminus. The MD simulations indicate that the strength of the interaction varies significantly between different enzyme conformations. [ABSTRACT FROM AUTHOR]

Ionic liquids (ILs) are a special class of low-temperature (typically < 100 °C) molten salts, which have huge upsurge interest in the field of chemical synthesis, catalysis, electrochemistry, pharmacology, and biotechnology, mainly due to their highly tunable nature and exceptional properties. However, practical uses of ILs are restricted mainly due to their adverse actions on organisms. Understanding interactions of ILs with biomembrane is prerequisite to assimilate the actions of these ionic compounds on the organism. Here, we review different biophysical methods to characterize interactions between ILs and phospholipid membrane, a model biomembrane. All these studies indicate that ILs interact profoundly with the lipid bilayer and modulate the structure, microscopic dynamics, and phase behavior of the membrane, which could be the fundamental cause of the observed toxicity of ILs. Effects of ILs on the membrane are found to be strongly dependent on the lipophilicity of the IL and are found to increase with the alkyl chain length of IL. This can be correlated with the observed higher toxicity of IL with the longer alkyl chain length. These informations would be useful to tune the toxicity of IL which is required in designing environment-friendly nontoxic solvents of the so-called green chemistry for various practical applications. [ABSTRACT FROM AUTHOR]

Detailed investigation of Cu (II) binding with natural lipid phosphatidylglycerol (PG) in aqueous solution was carried out by voltammetric measurements at the mercury drop electrode, complemented by monolayer studies in a Langmuir trough and electrophoretic measurements, all used as models for hydrophobic cell membranes. Penetration of copper ions into the PG layer was facilitated by the formation of hydrophilic Cu-Phenanthroline (Phen) complex in the subphase, followed by the mixed ligand Cu-Phen-PG complex formation at the hydrophobic interface. Electrophoretic measurements indicated a comparatively low abundance of the formed mixed ligand complex within the PG vesicles, resulting it the zeta potential change of + 0.83 mV, while monolayer studies confirmed their co-existence at the interface. The Cu-Phen-PG complex was identified in the pH range from 6 to 9. The stoichiometry of the complex ([PhenCuOHPG]), as well as its stability and kinetics of formation, were determined at the mercury drop electrode. Cu-Phen-PG reduces quasireversibly at about − 0.7 V vs. Ag/AgCl including reactant adsorption, followed by irreversible mixed complex dissociation, indicating a two-electron transfer - chemical reaction (EC mechanism). Consequently, the surface concentration ( γ ) of the adsorbed [PhenCuOHPG] complex at the hydrophobic electrode surface was calculated to be (3.35 ± 0.67) × 10 − 11 mol cm − 2 . Information on the mechanism of Cu (II) - lipid complex formation is a significant contribution to the understanding of complex processes at natural cell membranes. [ABSTRACT FROM AUTHOR]

Heat shock proteins of 90 kDa (Hsp90) are molecular chaperones essential for protein homeostasis. Besides chaperone activity, Hsp90 exhibits other cellular functions at membranes, yet how it interacts with membranes remains elusive. We report here that Hsp90B1 interacts with phospholipid membranes. We first cloned the full-length open reading frame of Hsp90B1 from Anas platyrhnchos (ApHsp90B1), and the gene was then heterologously expressed and purified. SPR analysis show the purified ApHsp90B1 interacts with phospholipid membranes with high affinity ( K D 176 ± 25 nM), and the interaction occurs over a wide range of pH, which is especially distinct under acidic conditions. Tryptophan fluorescence and far-UV CD spectra studies find that the interaction of ApHsp90B1 with phospholipid membrane induces microenvironment changes of tryptophan residues and conformational change of some regions in ApHsp90B1, which might be the reason of its increased ATPase activity upon addition phospholipid vesicles. Importantly, the interaction of ApHsp90B1 with phospholipid vesicles significantly reduces lipolysis of the membrane phospholipid, suggesting that the interaction of Hsp90B1 with membrane could preserve membrane integrity. The present study therefore demonstrates for the first time that Hsp90B1 exhibits high affinity for phospholipid membrane and suggest Hsp90B1 play an important role in membrane-stabilizing via its interaction with membrane phospholipids. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) may act by targeting the lipid membranes and disrupting the bilayer structure. In this study, three AMPs from the skin of Australian tree frogs, aurein 1.2, maculatin 1.1 and caerin 1.1, were investigated against Gram-negative Escherichia coli, Gram-positive Staphylococcus aureus, and vesicles that mimic their lipid compositions. Furthermore, equimolar mixtures of the peptides were tested to identify any synergistic interactions in antimicrobial activity. Minimum inhibition concentration and minimum bactericidal concentration assays showed significant activity against S. aureus but not against E. coli. Aurein was the least active while maculatin was the most active peptide and some synergistic effects were observed against S. aureus. Circular dichroism experiments showed that, in the presence of phospholipid vesicles, the peptides transitioned from an unstructured to a predominantly helical conformation (>50%), with greater helicity for POPG/TOCL compared to POPE/POPG vesicles. The helical content, however, was less in the presence of live E. coli and S. aureus, 25 and 5%, respectively. Equimolar concentrations of the peptides did not appear to form greater supramolecular structures. Dye release assays showed that aurein required greater concentration than caerin and maculatin to disrupt the lipid bilayers, and mixtures of the peptides did not cooperate to enhance their lytic activity. Overall, aurein, maculatin, and caerin showed moderate synergy in antimicrobial activity against S. aureus without becoming more structured or enhancement of their membrane-disrupting activity in phospholipid vesicles. [ABSTRACT FROM AUTHOR]

• Ethanol molecules disrupt the passage of calcium ions in the channel. • Diffusion coefficient in the absence of ethanol is 2500 nm2/ps and in the presence of ethanol it is 200 nm2/ps. • The flow of ions in the channels is controlled due to the presence of ethanol molecules. Drinking too much alcohol can lead to the development of chronic diseases and other serious problems including: heart disease, high blood pressure, stroke, digestive problems and liver disease. Over the past two decades, researchers have confirmed that ethanol is the primary agent in altering the function of voltage-gated calcium channels that lead to clock responses and behavioral responses to alcohol. In this study, the ethanol influence on calcium channel operation has been studied by molecular dynamics simulation of L-type calcium channels in the presence and absence of ethanol. Density, radius distribution, average potential force, radius gyration, pore radius, root mean square deviation and root mean square fluctuation are the performed analysis in this study. According to the results obtained; Ethanol blocks the calcium channel and interferes with calcium ions passage. Also, calcium ions show a greater tendency to interact with the residues inside the protein channel in the presence of ethanol. [ABSTRACT FROM AUTHOR]

Cyanidin and its O-glycosides have many important physiological functions in plants and beneficial effects on human health. Their biological activity is not entirely clear and depends on the structure of the molecule, in particular, on the number and type of sugar substituents. Therefore, in this study the detailed structure-activity relationship (SARs) of the anthocyanins/anthocyanidins in relation to their interactions with lipid bilayer was determined. On the basis of their antioxidant activity and the changes induced by them in size and Zeta potential of lipid vesicles, and mobility and order of lipid acyl chains, the impact of the number and type of sugar substituents on the biological activity of the compounds was evaluated. The obtained results have shown, that 3-O-glycosylation changes the interaction of cyanidin with lipid bilayer entirely. The 3-O-glycosides containing a monosaccharide induces greater changes in physical properties of the lipid membrane than those containing disaccharides. The presence of additional sugar significantly reduces glycoside interaction with model lipid membrane. Furthermore, O-glycosylation alters the ability of cyanidin to scavenge free radicals. This alteration depends on the type of free radicals and the sensitivity of the method used for their determination.

In this study, we have used liquid crystals (LCs) to investigate the mechanism and dynamics of structural change of phospholipid membranes caused by sodium deoxycholate (NaDC). Addition of the NaDC aqueous solution to the phospholipid [1,2-dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt (DOPG)] modified aqueous/LC interface resulted in the interaction-induced change of the orientational arrangement of the LCs from a homeotropic state to a planar state. The importance of contributing parameters was determined by observing the changes in the orientation of LCs. We showed that this interaction was affected by reaction time, reaction pH, concentration of NaDC and the presence of cholesterol. Moreover, the phospholipid membrane, which became defective after being exposed to NaDC, was capable of self-repairing by excess Tris-buffered saline solution, indicating that the reaction of NaDC with the phospholipid membrane is reversible. The obtained results proved the feasibility of the method deploying the DOPG/LC interface to monitor the membrane reaction stemming from the interaction between a bioactive molecule and a phospholipid membrane. [ABSTRACT FROM AUTHOR]

This paper reports on voltammetric methods applied in studies of transport processes connected with the occurrence of toxic cadmium in plants. As a means of transport across model of phospholipid membrane (PLM), calcium ionophore (calcimycin), cell-penetrating peptides (transportan 10 and mastoparan), and finally protoplasts isolated from barley roots and leaves were used. Using calcimycin, different influences of Cd complexation by citric acid or by malic acid as examples of root exudates were documented. For transport of simplest phytochelatin PC2, voltammetric methods using formation of Hg complex on hanging mercury drop electrode (HMDE) or of Ag complex on mercury meniscus covered silver solid amalgam electrode (m-AgSAE) were assessed. [ABSTRACT FROM AUTHOR]

Free docosahexaenoic acid (DHAn-3) and gamma linolenic acid (GLAn-6) effects on dimyristoyl phosphatidylcholine (DMPC) membranes were studied as a function of temperature by electron paramagnetic resonance (EPR) spectroscopy. 5- and 16-doxyl stearic acid (5-, 16-DS) spin labels were utilized to obtain information from the interfacial and alkyl chain region, respectively. In the studied temperature range, the presence of DHAn-3 or GLAn-6 caused decreases in maximum hyperfi ne splitting values and correlation times of DMPC membranes. Both in the interfacial region and depths of membrane, changes were more pronounced for DHAn-3 in pure DMPC. In the presence of cholesterol (CH), DHAn-3 and GLAn-6 effects were similar and more pronounced in the depths of the membrane. The changes in the structure and dynamics of samples were obtained from simulations of spectra, which indicated some changes in the number of spectral components by incorporation of DHAn-3 and GLAn-6. In the interfacial region and below the main phase transition temperature of DMPC, there was an increase in heterogeneity. For temperatures above the phase transition, a more homogeneous environment for spin label was obtained in the presence of fatty acids. [ABSTRACT FROM AUTHOR]