Lipid bilayer-atomic force microscopy combined platform records simultaneous electrical and topological changes of the TRP channel polycystin-2 (TRPP2).

Ion channels are transmembrane proteins that mediate ion transport across biological membranes. Ion channel function is traditionally characterized by electrical parameters acquired with techniques such as patch-clamping and reconstitution in lipid bilayer membranes (BLM) that provide relevant information such as ionic conductance, selectivity, and gating properties. High resolution structural information of ion channels however, requires independent technologies, of which atomic force microscopy (AFM) is the only one that provides topological features of single functional channel proteins in their native environments. To date practically no data exist on direct correlations between electrical features and topological parameters from functional single channel complexes. Here, we report the design and construction of a BLM reconstitution microchamber that supports the simultaneous recording of electrical currents and AFM imaging from single channel complexes. As proof-of-principle, we tested the technique on polycystin-2 (PC2, TRPP2), a TRP channel family member from which we had previously elucidated its tetrameric topology by AFM imaging, and single channel currents by the BLM technique. The experimental setup provided direct structural-functional correlates from PC2 single channel complexes that disclosed novel topological changes between the closed and open sub-conductance states of the functional channel, namely, an inverse correlation between conductance and height of the channel. Unexpectedly, we also disclosed intrinsic PC2 mechanosensitivity in response to external forces. The platform provides a suitable means of accessing topological information to correlate with ion channel electrical parameters essential to understand the physiology of these transmembrane proteins.

AgBr and AgCl nanoparticle doped TEMPO-oxidized microfiber cellulose as a starting material for antimicrobial filter.

Present work covers the state-of-art progress in the advanced nanoarchitecture of organic-inorganic hybrid material; a starting material for the antimicrobial filter. TEMPO-mediated oxidation of microfiber cellulose was carried out to introduce the surface active carboxyl groups. Accordingly, qualitative and quantitative substitution of a functional group was investigated using FTIR, Solid state 13C CP/MAS NMR, and potentiometric titration; the reaction resulted to about 21.06% increase in carboxylate content. Further, the microwave irradiated (600 W) in-situ synthesis of AgBr and AgCl nanocubes were prepared and doped on carboxylated microfiber. The prepared AgBr@TO-MF and AgCl@TO-MF were tested using XRD, XPS, SEM and FTIR. With an average size of AgBr and AgCl nanocubes of around 200 ±â€¯28 nm and 116 ±â€¯10.73 nm. Whereas, AgBr@TO-MF and AgCl@TO-MF shown excellent antimicrobial activity against E. Coli and B. Subtilis, with MIC at around 200 µg/mL and 150 µg/mL, respectively. Fascinatingly, ICP-OES analysis estimated the silver leached was around 0.1 ppm.

Nanoparticles for hyperthermic therapy: synthesis strategies and applications in glioblastoma.

Glioblastoma multiforme (GBM) is the most common and most aggressive malignant primary brain tumor in humans. Current GBM treatment includes surgery, radiation therapy, and chemotherapy, sometimes supplemented with novel therapies. Despite recent advances, survival of GBM patients remains poor. Major challenges in GBM treatment are drug delivery across the blood-brain barrier, restriction of damage to healthy brain tissues, and limitation of resistance to therapies. This article reviews recent advances in the application of magnetic nanoparticles (MNPs), gold nanorods (GNRs), and carbon nanotubes (CNTs) for hyperthermia ablation of GBM. First, the article introduces GBM, its current treatment, and hyperthermia as a potential modality for the management of GBM. Second, it introduces MNPs, GNRs, and CNTs as inorganic agents to induce hyperthermia in GBM. Third, it discusses different methodologies for synthesis of each inorganic agent. Finally, it reviews in vitro and in vivo studies in which MNPs, GNRs, and CNTs have been applied for hyperthermia ablation and drug delivery in GBM.

Beneficial effects of lysosome-modulating and other pharmacological and nanocarrier agents on amyloid-beta-treated cells.

The progression of Alzheimer's disease (AD) is accompanied by disturbances of the endosome/lysosome (EL) system and there is accumulation of peptides of the AD-associated amyloid beta (Abeta) type in EL vesicles of affected neurons. EL modulating agents partially ameliorate the Abeta-mediated cell abnormalities. However, no extensive studies on the potential pharmaceutical applications of combinations of such agents and their synergistic effects have been performed. This study shows the beneficial anti-amyloid effects of several combinations of lysosomal modulators and other pharmacological and new nanobiotechnological agents. Some agents potentiated each other's action and some of them facilitated the anti-amyloid actions of memantine, a modifier of Ca2+-permeable channels involved in AD and one of the few drugs used for treatment of AD. Another compound used in nanobiotechnology ameliorated as a nanocarrier the beneficial effects of some of these potential pharmaceutical agents. They may be considered as additional drugs to improve the efficacy of the therapeutic approaches for AD and related neurodegenerative disorders.