On the Mechanism of Membrane Permeabilization by Tamoxifen and 4-Hydroxytamoxifen.

Tamoxifen (TMX), commonly used in complementary therapy for breast cancer, also displays known effects on the structure and function of biological membranes. This work presents an experimental and simulation study on the permeabilization of model phospholipid membranes by TMX and its derivative 4-hydroxytamoxifen (HTMX). TMX induces rapid and extensive vesicle contents leakage in phosphatidylcholine (PC) liposomes, with the effect of HTMX being much weaker. Fitting of the leakage curves for TMX, yields two rate constants, corresponding to a fast and a slow process, whereas in the case of HTMX, only the slow process takes place. Interestingly, incorporation of phosphatidylglycerol (PG) or phosphatidylethanolamine (PE) protects PC membranes from TMXinduced permeabilization. Fourier-transform infrared spectroscopy (FTIR) shows that, in the presence of TMX there is a shift in the νCH2 band frequency, corresponding to an increase in gauche conformers, and a shift in the νC=O band frequency, indicating a dehydration of the polar region. A preferential association of TMX with PC, in mixed PC/PE systems, is observed by differential scanning calorimetry. Molecular dynamics (MD) simulations support the experimental results, and provide feasible explanations to the protecting effect of PG and PE. These findings add new information to explain the various mechanisms of the anticancer actions of TMX, not related to the estrogen receptor, and potential side effects of this drug.

Effects of a Semisynthetic Catechin on Phosphatidylglycerol Membranes: A Mixed Experimental and Simulation Study.

Catechins have been shown to display a great variety of biological activities, prominent among them are their chemo preventive and chemotherapeutic properties against several types of cancer. The amphiphilic nature of catechins points to the membrane as a potential target for their actions. 3,4,5-Trimethoxybenzoate of catechin (TMBC) is a modified structural analog of catechin that shows significant antiproliferative activity against melanoma and breast cancer cells. Phosphatidylglycerol is an anionic membrane phospholipid with important physical and biochemical characteristics that make it biologically relevant. In addition, phosphatidylglycerol is a preeminent component of bacterial membranes. Using biomimetic membranes, we examined the effects of TMBC on the structural and dynamic properties of phosphatidylglycerol bilayers by means of biophysical techniques such as differential scanning calorimetry, X-ray diffraction and infrared spectroscopy, together with an analysis through molecular dynamics simulation. We found that TMBC perturbs the thermotropic gel to liquid-crystalline phase transition and promotes immiscibility in both phospholipid phases. The modified catechin decreases the thickness of the bilayer and is able to form hydrogen bonds with the carbonyl groups of the phospholipid. Experimental data support the simulated data that locate TMBC as mostly forming clusters in the middle region of each monolayer approaching the carbonyl moiety of the phospholipid. The presence of TMBC modifies the structural and dynamic properties of the phosphatidylglycerol bilayer. The decrease in membrane thickness and the change of the hydrogen bonding pattern in the interfacial region of the bilayer elicited by the catechin might contribute to the alteration of the events taking place in the membrane and might help to understand the mechanism of action of the diverse effects displayed by catechins.

Anticancer drugs tamoxifen and 4hydroxytamoxifen as effectors of phosphatidylethanolamine lipid polymorphism.

The interaction of tamoxifen (TMX) and its metabolite 4-hydroxytamoxifen (HTMX) with a biomimetic membrane model system composed of 1,2-dielaidoylphosphatidylethanolamine (DEPE) has been studied using a biophysical approach. Incorporation of TMX into DEPE bilayers gives rise to a progressive broadening of the Lß/Lα phase transition and a downward temperature shift. The Lß/Lα phase transition presents multiple endotherms, indicating a lateral segregation of TMX/DEPE domains within the plane of the bilayer. TMX and HTMX also widen and shift the Lα to hexagonal-HII transition toward lower values, the phase diagrams showing that both compounds facilitate formation of the HII phase. TMX increases motional disorder of DEPE acyl chains in the Lß, Lα and HII phases, whereas the effect of HTMX is clearly different. In addition, neither TMX nor HTMX significantly perturb the hydration state of the polar headgroup region of DEPE. Molecular dynamics (MD) simulations indicate that these drugs do not affect membrane thickness, area per lipid, or the conformation of DEPE molecules. As a general rule, the interaction of HTMX with DEPE is qualitatively similar to TMX but less intense. However, a significant difference shown by MD is that HTMX is mainly placed around the center of each monolayer while TMX is located mainly at the center of the membrane, also having a greater tendency to cluster formation. These results are discussed to understand the modulation of phosphatidylethanolamine lipid polymorphism carried out by these drugs, which could be of relevance to explain their effects on enzyme activity or membrane permeabilization.

3,4,5-Trimethoxybenzoate of Catechin, an Anticarcinogenic Semisynthetic Catechin, Modulates the Physical Properties of Anionic Phospholipid Membranes.

3,4,5-Trimethoxybenzoate of catechin (TMBC) is a semisynthetic catechin which shows strong antiproliferative activity against malignant melanoma cells. The amphiphilic nature of the molecule suggests that the membrane could be a potential site of action, hence the study of its interaction with lipid bilayers is mandatory in order to gain information on the effect of the catechin on the membrane properties and dynamics. Anionic phospholipids, though being minor components of the membrane, possess singular physical and biochemical properties that make them physiologically essential. Utilizing phosphatidylserine biomimetic membranes, we study the interaction between the catechin and anionic bilayers, bringing together a variety of experimental techniques and molecular dynamics simulation. The experimental data suggest that the molecule is embedded into the phosphatidylserine bilayers, where it perturbs the thermotropic gel to liquid crystalline phase transition. In the gel phase, the catechin promotes the formation of interdigitation, and in the liquid crystalline phase, it decreases the bilayer thickness and increases the hydrogen bonding pattern of the interfacial region of the bilayer. The simulation data agree with the experimental ones and indicate that the molecule is located in the interior of the anionic bilayer as monomer and small clusters reaching the carbonyl region of the phospholipid, where it also disturbs the intermolecular hydrogen bonding between neighboring lipids. Our observations suggest that the catechin incorporates well into phosphatidylserine bilayers, where it produces structural changes that could affect the functioning of the membrane.

Interaction of Docetaxel with Phosphatidylcholine Membranes: A Combined Experimental and Computational Study.

The antineoplastic drug Docetaxel is a second generation taxane which is used against a great variety of cancers. The drug is highly lipophilic and produces a great array of severe toxic effects that limit its therapeutic effectiveness. The study of the interaction between Docetaxel and membranes is very scarce, however, it is required in order to get clues in relation with its function, mechanism of toxicity and possibilities of new formulations. Using phosphatidylcholine biomimetic membranes, we examine the interaction of Docetaxel with the phospholipid bilayer combining an experimental study, employing a series of biophysical techniques like Differential Scanning Calorimetry, X-Ray Diffraction and Infrared Spectroscopy, and a Molecular Dynamics simulation. Our experimental results indicated that Docetaxel incorporated into DPPC bilayer perturbing the gel to liquid crystalline phase transition and giving rise to immiscibility when the amount of the drug is increased. The drug promotes the gel ripple phase, increasing the bilayer thickness in the fluid phase, and is also able to alter the hydrogen-bonding interactions in the interfacial region of the bilayer producing a dehydration effect. The results from computational simulation agree with the experimental ones and located the Docetaxel molecule forming small clusters in the region of the carbon 8 of the acyl chain palisade overlapping with the carbonyl region of the phospholipid. Our results support the idea that the anticancer drug is embedded into the phospholipid bilayer to a limited amount and produces structural perturbations which might affect the function of the membrane.

Dissimilar action of tamoxifen and 4-hydroxytamoxifen on phosphatidylcholine model membranes.

The anticancer drug tamoxifen and its primary metabolite 4-hydroxytamoxifen tend to accumulate in membranes due to its strong hydrophobic character. Thus, in this work we have carried out a systematic study to investigate their effects on model phosphatidylcholine membranes. Tamoxifen and 4-hydroxytamoxifen affect the phase behaviour of phosphatidylcholine model membranes, giving rise to formation of drug/dipalmitoylphosphatidylcholine domains, which is more evident in the case of 4-hydroxytamoxifen. These drugs have differential effects on the polar and apolar regions of the phospholipid supporting a different location of both compounds within the bilayer. Both compounds induce contents leakage in fluid phosphatidylcholine unilamellar liposomes, the effect of 4-hydroxytamoxifen being negligible as compared to that of tamoxifen. Molecular dynamics confirmed the tendency of both drugs to form clusters, tamoxifen locating all along the bilayer, whereas 4-hydroxytamoxifen mostly locates near the lipid/water interface, which can explain the different effects of both drugs in fluid phosphatidylcholine membranes.

Effect of pH and temperature on the aggregation behaviour of dirhamnolipid biosurfactant. An experimental and molecular dynamics study.

HYPOTHESIS: Pseudomonas aeruginosa dirhamnolipid (diRL) has been shown to form aggregates of different size and structure, under various conditions. Due to the presence of a carboxyl group in the molecule, it is expected that pH would strongly affect this aggregation behaviour. In addition, preliminary observations of temperature-induced changes in the states of aggregation of diRL supported the need of further investigation. EXPERIMENTS: A systematic experimental study, using differential scanning calorimetry (DSC), small-angle Xray diffraction (SAXD), and Fourier-transform infrared spectroscopy (FTIR), has been carried out to characterize pH and temperature driven changes in the aggregation behavior of diRL biosurfactant. Molecular dynamics (MD) simulations, supported by the experimental results, allowed depicting molecular details on formation of diRL membranes and other aggregated structures under various physicochemical conditions. FINDINGS: DiRL could adopt fairly organized multilayered structures (membranes) at low pH and temperature, which became highly disordered upon increasing either of these parameters. The effect of pH on the gauche/all-trans conformer ratio of the diRL acyl chains was not of significance, whereas temperature-induced effects were observed. For the first time it is described that diRL underwent an endothermic thermotropic transition with Tc = 34 °C as observed by DSC, at pH 4.5 (protonated diRL), but not at pH 7.4 (unprotonated diRL). FTIR confirmed these findings, showing a significant additional disordering of the all-trans acyl chains upon increasing temperature around that same value in the protonated form, an effect not observed for the dissociated form of the biosurfactant. In addition, at pH 7.4, changing temperature did not modify the hydration state of the polar moiety of diRL, whereas at pH 4.5 a significant decrease in the hydration state around 34 °C took place. SAXD data showed that protonated diRL formed multilayered structures at 20 °C, which converted into poorly correlated layers at 50 °C. MD simulations supported these findings, showing that the membrane-like structures formed by protonated diRL at 20 °C became unstable at higher temperatures, tending to form other structures, which could be micelles or other type of layered structures, whereas the negatively charged form of diRL organized in micelle-type aggregates in the whole range of temperature under study.

Interaction of a dirhamnolipid biosurfactant with sarcoplasmic reticulum calcium ATPase (SERCA1a).

The interaction of a dirhamnolipid biosurfactant secreted by Pseudomonas aeruginosa with calcium ATPase from sarcoplasmic reticulum (SR) was studied by means of different approaches, such as enzyme activity, fluorescence spectroscopy, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and molecular docking simulations. The ATP hydrolysis activity was fully inhibited by incubation with dirhamnolipid (diRL) up to 0.1 mM concentration, corresponding to a surfactant concentration below membrane solubilization threshold. Surfactant-protein interaction induced conformational changes in the protein observed by an increase in the accessibility of tryptophan residues to the aqueous phase and by changes in the secondary structure of the protein as seen by fluorescence and FTIR spectroscopy. As a consequence, the protein become more unstable and denatured at lower temperatures, as seen by enzyme activity and DSC studies. Finally, these results were explained at molecular level throughout molecular docking simulations. It is concluded that there is a specific dirhamnolipid-protein interaction not related to the surface activity of the surfactant but to the particular physicochemical properties of the biosurfactant molecule.

Effect of a dirhamnolipid biosurfactant on the structure and phase behaviour of dimyristoylphosphatidylserine model membranes.

Rhamnolipids are bacterial biosurfactants containing one or two rhamnose rings and a hydrophobic hydrocarbon portion. These compounds are mainly isolated from Pseudomonas spp culture media, and have been shown to present outstanding biological activities. A number of experimental works have shown that the interaction of rhamnolipids with target membranes could play a role in these actions. Therefore the study of the interaction of purified rhamnolipids with the various phospholipid components of biological membranes is of great interest. This paper shows the phase behaviour of mixtures of 1,2-dimyristolylphosphatidylserine (DMPS) with a dirhamnolipid (diRL) fraction produced by P. aeruginosa. This experimental approach has been based on the use of physical techniques such as Differential Scanning Calorimetry (DSC) and Fourier-Transform Infrared Spectroscopy (FTIR). DSC indicated that the presence of increasing concentrations of diRL in the bilayer resulted in a progressive broadening of the gel to liquid-crystalline phase transition of DMPS. In addition a complex thermal behaviour was observed, with the presence of more than one transition at higher concentrations of the biosurfactant, indicating phase separation. FTIR showed that diRL increased the proportion of gauche rotamers of DMPS, thus affecting acyl chain order. The change in the frequency of the carboxylate stretching band of DMPS observed upon interaction with diRL pointed toward changes in the local environment of the polar headgroup of the phospholipid, resulting in a modification of its conformation or insertion within the bilayer. This result was corroborated by the effect of diRL on the carbonyl and phosphate stretching bands of DMPS, showing an increase of the hydration both in the gel and in the liquid-crystalline phase. Molecular Dynamics (MD) simulations gave further support to the experimental results, showing diRL cluster formation as well as an augmented exposition of DMPS to the water layer in the presence of the biosurfactant.

Parallel sorting of orbital and spin angular momenta of light in a record large number of channels.

Parallel sorting of orbital and spin angular momentum components of structured optical beams is demonstrated. Both spin channels are multiplexed within the novel orbital angular momentum (OAM) sorter, reducing the size, weight, and number of elements. The sorted states are linearly spaced over 70 topological charge values. We experimentally and theoretically evaluate the operational range and crosstalk between neighboring channels and find that 30 orbital angular momentum states are available per spin channel for quantum communication or cryptography. This is achieved using an angular momentum sorter that we developed based on geometric phase optical elements. We present two devices consisting of liquid crystal polymer films photoaligned with complex two-dimensional patterns.

Interaction of the Lipopeptide Biosurfactant Lichenysin with Phosphatidylcholine Model Membranes.

Lichenysins produced by Bacillus licheniformis are anionic lipopeptide biosurfactants with cytotoxic, antimicrobial, and hemolytic activities that possess enormous potential for chemical and biological applications. Through the use of physical techniques such as differential scanning calorimetry, small- and wide-angle X-ray diffraction, and Fourier-transform infrared spectroscopy as well as molecular dynamics simulations, we report on the interaction of Lichenysin with synthetic phosphatidylcholines differing in hydrocarbon chain length. Lichenysin alters the thermotropic phase behavior of phosphatidylcholines, displaying fluid-phase immiscibility and showing a preferential partitioning into fluid domains. The interlamellar repeat distance of dipalmitoylphosphatidylcholine (DPPC) is modified, affecting both the phospholipid palisade and the lipid/water interface, which also experiences a strong dehydration. Molecular dynamics confirms that Lichenysin is capable of interacting both with the hydrophobic portion of DPPC and with the polar headgroup region, which is of particular relevance to explain much of its properties. The results presented here help to establish a molecular basis for the Lichenysin-induced perturbation of model and biological membranes previously described in the literature.

The increase in positively charged residues in cecropin D-like Galleria mellonella favors its interaction with membrane models that imitate bacterial membranes.

A comparative study of three synthetic peptides, namely neutral Cecropin D-like G. mellonella (WT) and two cationic peptides derived from its sequence, ΔM1 (+5) and ΔM2 (+9) is reported in this work. The influence of charge on the interactions between peptides and membranes and its effect on phase were studied by calorimetric assays. Differential scanning calorimetry (DSC) showed that ΔM2 peptide showed the strongest effect when the membrane contained phosphatidylcholine (PC) and phosphatidylglycerol (PG), increasing membrane fluidization. Fourier transform infrared spectroscopy (FTIR) was used to determine lipid segregation in the presence of peptides. When WT and ΔM1 bound to model membrane containing PG and PC (1:1 molar ratio) a separation of both lipids was observed. Meanwhile, ΔM2 peptide also induced a demixing of PG-peptide rich domains separated from PC. FTIR experiments also suggested that the presence of ΔM1 and ΔM2 peptides increased lipid carbonyl group hydration in DMPG membrane fluid phase, However, hydration at the interface level in fluid phase was notably increased in the presence of WT and ΔM1 peptides in DMPC/DMPG. Overall the increase in positively charged residues favors the interaction of the peptides with the negatively charged membrane and its perturbation.

The vertical location of α-tocopherol in phosphatidylcholine membranes is not altered as a function of the degree of unsaturation of the fatty acyl chains.

α-Tocopherol is a natural preservative that prevents free radical chain oxidations in biomembranes. We have studied the location of α-tocopherol in model membranes formed by different unsaturated phosphatidylcholines, namely 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine (PLPC), 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC) and 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (PDPC). Small angle X-ray diffraction revealed that α-tocopherol was well mixed with all the phospholipids. In all the cases only one lamellar phase was detected. Very modest changes occasioned by α-tocopherol were observed in the electron density profiles. The results obtained from quenching of α-tocopherol intrinsic fluorescence by acrylamide showed that this vitamin was inefficiently quenched in the four types of membranes, indicating that the fluorescent chromanol ring was poorly accessible for this hydrophilic quencher. Compatible with that, quenching by doxyl derivatives of phosphatidylcholines indicated that the chromanol ring was close in the four membranes to the nitroxide probe located at position 5. Quenching by doxyl-phosphatidylcholines also indicated that the efficiency of quenching was higher in POPC than in the other unsaturated phospholipids. 1H-MAS-NMR showed that α-tocopherol induced chemical shifts of protons from the phospholipids, especially of those bonded to carbons 2 and 3 of the acyl chains of the four phospholipids studied. The 1H-MAS-NMR NOESY results suggested that the lower part of the chromanol ring was located between the C3 of the fatty acyl chains and the centre of the hydrophobic monolayer for the four phospholipid membranes studied. Taken together, these results suggest that α-tocopherol is located, in all the membranes studied, with the chromanol ring within the hydrophobic palisade but not far away from the lipid-water interface.

Location and Effects of an Antitumoral Catechin on the Structural Properties of Phosphatidylethanolamine Membranes.

Green tea catechins exhibit high diversity of biological effects including antioncogenic properties, and there is enormous interest in their potential use in the treatment of a number of pathologies. It is recognized that the mechanism underlying the activity of catechins relay in part in processes related to the membrane, and many studies revealed that the ability of catechins to interact with lipids plays a probably necessary role in their mechanism of action. We present in this work the characterization of the interaction between an antitumoral synthetically modified catechin (3-O-(3,4,5-trimethoxybenzoyl)-(-)-catechin, TMCG) and dimiristoylphosphatidyl-ethanolamine (DMPE) membranes using an array of biophysical techniques which include differential scanning calorimetry, X-ray diffraction, infrared spectroscopy, atomic force microscopy, and molecular dynamics simulations. We found that TMCG incorporate into DMPE bilayers perturbing the thermotropic transition from the gel to the fluid state forming enriched domains which separated into different gel phases. TMCG does not influence the overall bilayer assembly of phosphatidylethanolamine systems but it manages to influence the interfacial region of the membrane and slightly decrease the interlamellar repeat distance of the bilayer. TMCG seems to be located in the interior of the phosphatidylethanolamine bilayer with the methoxy groups being in the deepest position and some portion of the molecule interacting with the water interface. We believe that the reported interactions are significant not only from the point of view of the known antitumoral effect of TMCG, but also might contribute to understanding the basic molecular mechanism of the biological effects of the catechins found at the membrane level.

Kinetic and Structural Aspects of the Permeabilization of Biological and Model Membranes by Lichenysin.

The various lichenysins produced by Bacillus licheniformis are anionic surfactants with interesting properties. Here it is shown that lichenysin caused hemolysis of human erythrocytes, which varied with lichenysin concentration in a sigmoidal manner. The release of K(+) from red blood cells induced by lichenysin preceded the leakage of hemoglobin, and in addition, hemolysis could be impeded by the presence of compounds in the external medium having a size larger than that of PEG 3350, indicating a colloid-osmotic mechanism for hemolysis. Lichenysin also caused permeabilization of model phospholipid membranes, which was a slow process with an initial lag period of 10-20 s observed for all lichenysin concentrations. A high cholesterol ratio in the membrane decreased the extent of leakage as compared to that of pure POPC, whereas at lower ratios the effect of cholesterol was the opposite, enhancing the extent of leakage. POPE was found to decrease the extent of leakage at all the concentrations assayed, and inclusion of DPPC resulted in a considerable increase in CF leakage extent. From this scenario it was concluded that lipid membrane composition plays a role in the target membrane selectivity of lichenysin. Molecular dynamics simulations indicated that lichenysin is well distributed along the bilayer, and Na(+) ions can penetrate inside the bilayer through the lichenysin molecules. The presence of lichenysin in the membrane increases the permeability of the membrane to hydrophilic molecules facilitating its flux across the lipid palisade. The results presented in this work contribute to understanding the molecular mechanisms that explain the biological actions of lichenysin related to biomembranes.

Kinetic characterization of Ca²âº-ATPase (SERCA1) inhibition by tri-n-butyltin(IV) chloride. A docking conformation proposal.

Organotin compounds, such as tri-n-butyltin(IV) chloride (TBT), are widespread toxicants which disrupt different functions in living organisms. TBT interacts with lipid membranes and membrane proteins. The inhibition of the calcium ATPase from sarcoplasmic reticulum membranes by TBT was studied. It was found that the ATPase inhibition could not be reverted in a large time scale; moreover, an excess of TBT over enzyme did not fully inhibit the ATPase activity; therefore, it was concluded that TBT irreversibly inhibits the enzyme, and this inhibition is accompanied by a decrease in the effective TBT concentration. The residual ATP hydrolysis activity was measured at different TBT concentrations with time, and the protective effect of different calcium concentrations on the TBT inhibition was also determined. The simplest kinetic mechanism to successfully explain all the observations and the kinetic behavior was found to be a single irreversible step of the inhibitor binding to the enzyme accompanied with a first-order inhibitor inactivation. A fluorescence study of fluorescein-5-isothiocyanate-labeled enzyme revealed that TBT binding to the enzyme entails a conformational change related to the high- to low-affinity calcium-binding state transition (E1 to E2 transition), resembling the conformational change induced by vanadate linked to the formation of E2 V complex from E1 state. A docking study allowed us to propose a binding pocket for TBT in the membrane region of E1 close to the high-affinity calcium-binding sites, as well as to define the interactions with amino acid residues interfering with calcium sites occupancy.

Interactions of a bacterial trehalose lipid with phosphatidylglycerol membranes at low ionic strength.

Trehalose lipids are bacterial biosurfactants which present interesting physicochemical and biological properties. These glycolipids have a number of different commercial applications and there is an increasing interest in their use as therapeutic agents. The amphiphilic nature of trehalose lipids points to the membrane as their hypothetical site of action and therefore the study of the interaction between these biosurfactants and biological membranes is critical. In this study, we examine the interactions between a trehalose lipid (TL) from Rhodococcus sp. and dimyristoylphosphatidylglycerol (DMPG) membranes at low ionic strength, by means of differential scanning calorimetry, light scattering, fluorescence polarization and infrared spectroscopy. We describe that there are extensive interactions between TL and DMPG involving the perturbation of the thermotropic intermediate phase of the phospholipid, the destabilization and shifting of the DMPG gel to liquid crystalline phase transition to lower temperatures, the perturbation of the sample transparency, and the modification of the order of the phospholipid palisade in the gel phase. We also report an increase of fluidity of the phosphatidylglycerol acyl chains and dehydration of the interfacial region of the bilayer. These changes would increase the monolayer negative spontaneous curvature of the phospholipid explaining the destabilizing effect on the intermediate state exerted by this biosurfactant. The observations contribute to get insight into the biological mechanism of action of the biosurfactant and help to understand the properties of the intermediate phase display by DMPG at low ionic strength.

Tunable millimeter and sub-millimeter spectral response of textile metamaterial via resonant states.

We report on a new textile metamaterial created by adding metal wires directly into the polymer yarn. Split-ring resonator-like extended states are created. Simulations revealed that the extended states can be easily tuned via the geometry. Measurements of the transmittance spectrum as a function of the polarization angle in the low terahertz range were also performed and these peaks were ascribed to a polarization-dependent resonator model. The fabrics are viable candidates for flexible and deformable gigahertz and terahertz-enabled metamaterials.

Effects of a synthetic antitumoral catechin and its tyrosinase-processed product on the structural properties of phosphatidylcholine membranes.

Catechin flavonoids are the main components of green tea extracts which present broad potential physiological activities. Several of their biological activities seem to affect membrane-dependent cellular processes and it is known that some catechins interact with phospholipid membranes. In this study we examine the interactions of a 3-O-(3,4,5-trimethoxybenzoyl)-(-)-catechin (TMCG), and its quinone methide (QM) activated product with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) membranes by means of differential scanning calorimetry, X-ray diffraction, Fourier-Transform infrared spectroscopy and molecular dynamics simulation. We report that there are extensive interactions between TMCG and DPPC involving the perturbation of the thermotropic gel to liquid crystalline phase transition of the phospholipid, the decrease of bilayer thickness and the promotion of interdigitated gel phase, together with an increase of the hydrogen bonding pattern of the interfacial region of the bilayer. In contrast, QM shows a weak interaction with the phospholipid bilayer. Molecular dynamics simulation indicates that TMCG locates in the interior of the bilayer, while QM is found interacting with the surface of the membrane. The observations are interpreted in terms of the mechanism of membrane prodrug activation and the underlying membrane perturbations of the biological actions of natural catechins.

Interaction of a trehalose lipid biosurfactant produced by Rhodococcus erythropolis 51T7 with a secretory phospholipase A2.

Trehalose-containing glycolipid biosurfactants form an emerging group of interesting compounds, which alter the structure and properties of phospholipid membranes, and interact with enzymatic and non-enzymatic proteins. Phospholipases A2 constitute a class of enzymes that hydrolyze the sn-2 ester of glycerophospholipids, and are classified into secreted phospholipases A2 (sPLA2) and intracellular phospholipases A2. In this work, pancreatic sPLA2 was chosen as a model enzyme to study the effect of the trehalose lipid biosurfactant on enzymes acting on interfaces. By using this enzyme, it is possible to study the modulation of enzyme activity, either by direct interaction of the biosurfactant with the protein, or as a result of the incorporation of the glycolipid on the phospholipid target membrane. It is shown that the succinoyl trehalose lipid isolated from Rhodococcus erythropolis 51T7 interacts with porcine pancreatic sPLA2 and inhibits its catalytic activity. Two modes of inhibition are observed, which are clearly differentiated by its timescale. First, a slow inhibition of sPLA2 activity upon preincubation of the enzyme with trehalose lipid in the absence of substrate is described. Second, incorporation of trehalose lipid into the phospholipid target membrane gives rise to a fast enzyme inhibition. These results are discussed in the light of previous data on sPLA2 inhibitors and extend the list of interesting biological activities reported for this R. erythropolis trehalose lipid biosurfactant.