Glutamate Receptors and Glioblastoma Multiforme: An Old "Route" for New Perspectives

Glioblastoma multiforme (GBM) is the most aggressive malignant tumor of the central nervous system, with poor survival in both treated and untreated patients. Recent studies began to explain the molecular pathway, comprising the dynamic structural and mechanical changes involved in GBM. In this context, some studies showed that the human glioblastoma cells release high levels of glutamate, which regulates the proliferation and survival of neuronal progenitor cells. Considering that cancer cells possess properties in common with neural progenitor cells, it is likely that the functions of glutamate receptors may affect the growth of cancer cells and, therefore, open the road to new and more targeted therapies

Zno thin films growth optimization for piezoelectric application

The piezoelectric response of ZnO thin films in heterostructure-based devices is strictly related to their structure and morphology. We optimize the fabrication of piezoelectric ZnO to reduce its surface roughness, improving the crystalline quality, taking into consideration the role of the metal electrode underneath. The role of thermal treatments, as well as sputtering gas composition, is investigated by means of atomic force microscopy and x-ray diffraction. The results show an optimal reduction in surface roughness and at the same time a good crystalline quality when 75% O2 is introduced in the sputtering gas and deposition is performed between room temperature and 573 K. Subsequent annealing at 773 K further improves the film quality. The introduction of Ti or Pt as bottom electrode maintains a good surface and crystalline quality. By means of piezoelectric force microscope, we prove a piezoelectric response of the film in accordance with the literature, in spite of the low ZnO thickness and the reduced grain size, with a unipolar orientation and homogenous displacement when deposited on Ti electrode

Thermoelectric and Structural Properties of Sputtered AZO Thin Films with Varying Al Doping Ratios

Nanomaterials can be game-changers in the arena of sustainable energy production because they may enable highly efficient thermoelectric energy conversion and harvesting. For this purpose, doped thin film oxides have been proven to be promising systems for achieving high thermoelectric performances. In this work, the design, realization, and experimental investigation of the thermoelectric properties exhibited by a set of five Al:ZnO thin films with thicknesses of 300 nm and Al doping levels ranging from 2 to 8 at.% are described. Using a multi-technique approach, the main structural and morphological features of the grown thin films are addressed, as well as the electrical and thermoelectrical transport properties. The results show that the samples exhibited a Seebeck coefficient absolute value in the range of 22-33 mu V/K, assuming their maximum doping level was 8 at.%, while the samples' resistivity was decreased below 2 x 10(-3) Ohm center dot cm with a doping level of 3 at.%. The findings shine light on the perspectives of the applications of the metal ZnO thin film technology for thermoelectrics

Daptomycin Strongly Affects the Phase Behavior of Model Lipid Bilayers

Daptomycin (DAP) is a calcium-dependent cyclic lipopeptide with great affinity for negatively charged phospholipids bearing the phosphatidylglycerol (PG) headgroup and has been used since 2003 as a last resort antibiotic in the treatment of severe infections caused by Gram-positive bacteria. The first step of its mechanism of action involves the interaction with the bacterial membrane, which not only represents a physical barrier but also accommodates transmembrane proteins, such as receptors, transporters, and enzymes, whose activity is crucial for the survival of bacteria. This results in a less efficient development of resistance strategies by pathogens compared to common antibiotics that activate or inhibit biochemical pathways connected to specific target proteins. Although already on the market, the molecular mechanism of action of DAP is still a controversial subject of investigation and it is most likely the result of a combination of distinct effects. Understanding how DAP targets the membrane of pathogens could be of great help in finding its analogues that could better avoid the development of resistance. Here, exploiting fluorescence microscopy and atomic force microscopy (AFM), we demonstrated that DAP affects the thermodynamic behavior of lipid mixtures containing PG moieties. Regardless of whether the PG lipids are in the liquid or solid phase, DAP preferably interacts with this headgroup and is able to penetrate more deeply into the lipid bilayer in the regions where this headgroup is present. In particular, considering the results of an AFM/spectroscopy investigation, DAP appears to produce a stiffening effect of the domains where PG lipids are mainly in the fluid phase, whereas it causes fluidification of the domains where PG lipids are in the solid phase

AFM investigation of mechanical properties of glioblastoma multiforme cells and their relation to motility

Glial tumors are clinically classified in 4 groups according to their malignancy level. Glial tumors belonging to the IV group are called Glioblastoma Multiforme (GBM) and they are among the most aggressive brain tumors. In the recent years the mechanical phenotype of cells has been recognized as a valuable marker of their malignancy level [1-3]. Here we studied by AFM the mechanical behavior of U87mg cells when exposed to a drug which interferes with their cytoskeleton affecting also their migration ability. We found that U87mg cells exposed to the tested drug presented a decreased migration potential which is correlated with an increased stiffness of the cells and with a loss of polarity. By exploiting AFM Dynamic Mechanical Analysis we also characterized the behavior of the cells for different probing frequencies. By exploiting immunofluorescence microscopy we also investigated the effect of the tested drug on the reorganization of the cell cytoskeleton finding a strong increase of the presence of stress fibers

Magainin-H2 effects on the permeabilization and mechanical properties of giant unilamellar vesicles

Among the potential novel therapeutics to treat bacterial infections, antimicrobial peptides (AMPs) are a very promising substitute due to their broad-spectrum activity and rapid bactericidal action. AMPs strongly interact with the bacterial membrane, and the need to have a correct understanding of the interaction between AMPs and lipid bilayers at a molecular level prompted a wealth of experimental and theoretical studies exploiting a variety of AMPs. Here, we studied the effects of magainin H2 (Mag H2), an analog of the well-known magainin 2 (wt Mag 2) AMP endowed with a higher degree of hydrophobicity, on giant unilamellar vesicles (GUVs) concentrating on its permeabilization activity and the effect on the lipid bilayer mechanical properties. We demonstrated that the increased hydrophobicity of Mag H2 affects its selectivity conferring a strong permeabilization activity also on zwitterionic lipid bilayers. Moreover, when lipid mixtures including PG lipids are considered, PG has a protective effect, at variance from wt Mag 2, suggesting that for Mag H2 the monolayer curvature could prevail over the peptide-membrane electrostatic interaction. We then mechanically characterized GUVs by measuring the effect of Mag H2 on the bending constant of lipid bilayers by flickering spectroscopy and, by using micropipette aspiration technique, we followed the steps leading to vesicle permeabilization. We found that Mag H2, notwithstanding its enhanced hydrophobicity, has a pore formation mechanism compatible with the toroidal pore model similar to that of wt Mag 2

Properties and Membrane Distillation Performance of Polypropylene Porous Membranes

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