Aranda Martínez, Francisco José

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Aranda Martínez, Francisco José

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Aranda Martínez, Francisco José

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Universidad de Murcia. Departamento de Bioquímica y Biología MolecularA

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Open Access
Recent advances on the interaction of glycolipid and lipopeptide biosurfactants with model and biological membranes
(Elsevier, 2023-12) Terue, José A.; Aranda Martínez, Francisco José; Ortiz López, Antonio; Bioquímica y Biología Molecular A
Microbial biosurfactants have gained interest in the last de cades because of their unique characteristics. The variety of chemical structures within these compounds makes them very versatile, with glycolipids and lipopeptides outstanding among the rest. The amphiphilic nature of these compounds makes them to partition into and strongly interact with phospholipid membranes, modifying their structure and function. Thus, much research has been done on the characterization of the interaction of glycolipid and lipopeptide biosurfactants with model and biological membranes. Whereas the studies involving phospholipid model membranes were mostly carried out earlier, most of the recent research has focused on bio logical membranes, including mammalian and microorgan isms’ systems. This review presents the recent developments achieved on the interaction of the main glycolipid and lipo peptide biosurfactants with model and biological membranes.
Open Access
Optimization of Innovative Three-Dimensionally-Structured Hybrid Vesicles to Improve the Cutaneous Delivery of Clotrimazole for the Treatment of Topical Candidiasis
(MDPI, 2019-06-06) Manca, Maria Letizia; Usach, Iris; Esteban Peris, José; Ibba, Antonella; Orrù, Germano; Valenti, Donatella; Escribano-Ferrer, Elvira; Gomez-Fernandez, Juan Carmelo; Maria Fadda, Anna; Manconi, Maria; Aranda Martínez, Francisco José; Bioquímica y Biología Molecular A
New three-dimensionally-structured hybrid phospholipid vesicles, able to load clotrimazole in a high amount (10 mg/mL), were obtained for the first time in this work by significantly reducing the amount of water (≤10%), which was replaced with a mixture of glycerol and ethanol (≈90%). A pre-formulation study was carried out to evaluate the effect of both the composition of the hydrating medium and the concentration of the phospholipid on the physico-chemical properties of hybrid vesicles. Four different three-dimensionally-structured hybrid vesicles were selected as ideal systems for the topical application of clotrimazole. An extensive physico-chemical characterization performed using transmission electron microscopy (TEM), cryogenic transmission electron microscopy (cryo-TEM), 31P-NMR, and small-angle X-ray scattering (SAXS) displayed the formation of small, multi-, and unilamellar vesicles very close to each other, and was capable of forming a three-dimensional network, which stabilized the dispersion. Additionally, the dilution of the dispersion with water reduced the interactions between vesicles, leading to the formation of single unilamellar vesicles. The evaluation of the in vitro percutaneous delivery of clotrimazole showed an improved drug deposition in the skin strata provided by the three-dimensionally-structured vesicles with respect to the commercial cream (Canesten®) used as a reference. Hybrid vesicles were highly biocompatible and showed a significant antifungal activity in vitro, greater than the commercial cream Canesten®. The antimycotic efficacy of formulations was confirmed by the reduced proliferation of the yeast cells at the site of infection in vivo. In light of these results, clotrimazole-loaded, three-dimensionally-structured hybrid vesicles appear to be one of the most innovative and promising formulations for the treatment of candidiasis infections.
Open Access
Anticarcinogenic trimethoxybenzoate of catechin stabilizes the liquid crystalline bilayer phase in phosphatidylethanolamine membranes
(Elsevier, 2022-11-11) Aranda, Elisa; Teruel Puche, José Antonio; Ortiz López, Antonio; Pérez Cárceles, María Dolores; Rodríguez López, José Neptuno; Aranda Martínez, Francisco José; Bioquímica y Biología Molecular A
The anticarcinogenic properties of catechins stand out among the great variety of biological actions attributed to these compounds. The capacity of catechins to interact with lipids and their participation in membrane related processes points out to the membrane as their potential site of action. Phosphatidylethanolamine is an abundant phospholipid in mammalian membranes that has tendency to form non lamellar phases, it is associated with important cellular processes, and it has been related to cancer. In order to shed light into the molecular effect of the anticarcinogenic 3,4,5- trimethoxybenzoate of catechin (TMBC) on lipid polymorphism and membrane structure and dynamics, we present a combined experimental and computational study of the interaction between this semisyn thetic catechin and biomimetic membranes composed of unsaturated phosphatidylethanolamine. Our experimental evidence reveals that TMBC is readily incorporated into unsaturated phos phatidylethanolamine system where it is able to shift the gel to liquid crystalline phase transition tem perature to lower values, decreasing the cooperativity and the enthalpy change of the transition. The presence of TMBC is able to promote the formation of gel phase immiscibility and to block the formation of the inverted hexagonal pha se. In the bilayer liquid crystalline phase, the catechin decreases the inter lamellar repeat distance, it increases the fluidity of the membrane, and it alters the hydrogen bond pat tern of the interfacial region of the bilayer. Our molecular dynamics results concur with the experimental data and locate TMBC forming different domains near the interfacial region of the bilayer where it mod ifies the lateral pressure profile of the membrane leading to a stabilization of the bilayer in the liquid crystalline phase and to a potential alteration of the function of the membrane
Metadata only
Localización y dinámica del coenzima Q en membranas fosfolípidas: comparación con la vitamina E y el Ionoforo Lasalocido A. / Francisco José Aranda Martínez.
(Murcia : Universidad,, 1986) Aranda Martínez, Francisco José
Open Access
3,4,5-Trimethoxybenzoate of Catechin, an Anticarcinogenic Semisynthetic Catechin, Modulates the Physical Properties of Anionic Phospholipid Membranes
(MDPI, 2022-05-03) Aranda, Elisa; Aranda Martínez, Francisco José; Ortiz López, Antonio; Rodríguez López, José Neptuno; Teruel Puche, José Antonio; Pérez Cárceles, María Dolores; Bioquímica y Biología Molecular A
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 inter action 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 phos phatidylserine 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 phos phatidylserine bilayers, where it produces structural changes that could affect the functioning of the membrane
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Effect of pH and temperature on the aggregation behaviour of dirhamnolipid biosurfactant. An experimental and molecular dynamics study
(Elsevier, 2021-04-05) Ortiz, Julia; Oliva, Alfonso; Teruel Puche, José Antonio; Aranda Martínez, Francisco José; Ortiz López, Antonio; Bioquímica y Biología Molecular A
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 pectroscopy (FTIR), has been carried out to charac terize 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 organizedmultilayered 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 disso ciated 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 con verted 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, tend ing to form other structures, which could be micelles or other type of layered structures, whereas the nega tively charged form of diRL organized in micelle-type aggregates in the whole range of temperature under study.
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Effect of a dirhamnolipid biosurfactant on the structure and phase behaviour of dimyristoylphosphatidylserine model membranes
(2019-10-19) Oliva, Alfonso; Aranda Martínez, Francisco José; Ortiz López, Antonio; Teruel Puche, José Antonio; Bioquímica y Biología Molecular A
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 dir hamnolipid (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.
Open Access
Effects of a Semisynthetic Catechin on Phosphatidylglycerol Membranes: A Mixed Experimental and Simulation Study
(MDPI, 2023-01-03) Aranda, Elisa; Aranda Martínez, Francisco José; Ortiz López, Antonio; Rodríguez López, José Neptuno; Teruel Puche, José Antonio; Pérez Cárceles, María Dolores; Bioquímica y Biología Molecular A
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.