Genetic variation in neurodegenerative diseases and its accessibility in the model organism Caenorhabditis elegans.

BACKGROUND: Neurodegenerative diseases (NGDs) such as Alzheimer's and Parkinson's are debilitating and largely untreatable conditions strongly linked to age. The clinical, neuropathological, and genetic components of NGDs indicate that neurodegeneration is a complex trait determined by multiple genes and by the environment. MAIN BODY: The symptoms of NGDs differ among individuals due to their genetic background, and this variation affects the onset and progression of NGD and NGD-like states. Such genetic variation affects the molecular and cellular processes underlying NGDs, leading to differential clinical phenotypes. So far, we have a limited understanding of the mechanisms of individual background variation. Here, we consider how variation between genetic backgrounds affects the mechanisms of aging and proteostasis in NGD phenotypes. We discuss how the nematode Caenorhabditis elegans can be used to identify the role of variation between genetic backgrounds. Additionally, we review advances in C. elegans methods that can facilitate the identification of NGD regulators and/or networks. CONCLUSION: Genetic variation both in disease genes and in regulatory factors that modulate onset and progression of NGDs are incompletely understood. The nematode C. elegans represents a valuable system in which to address such questions.

Melanin-containing films: growth from dopamine solutions versus layer-by-layer deposition.

Films formed by oxidation of dopamine are of interest for functionalisation of solid-liquid interfaces owing to their versatility. However, the ability to modulate the properties of such films, for example, permeability to ionic species and the absorption coefficient, is urgently needed. Indeed, melanin films produced by oxidation of dopamine absorb strongly over the whole UV/Vis part of the electromagnetic spectrum and are impermeable to anions even for a film thickness as low as a few nanometers. Herein we combine oxidation of dopamine to produce a solution containing dopamine-melanin particles and their alternating deposition with poly(diallyldimethylammonium chloride) to produce films which have nearly the same morphology as pure dopamine-melanin films but are less compact, more transparent and more permeable to ferrocyanide anions.

Chiral luminescent CdS nano-tetrapods.

The utilisation of chiral penicillamine stabilisers allowed the preparation of new water soluble white emitting CdS nano-tetrapods, which demonstrated circular dichroism in the band-edge region of the spectrum.

Transparent conductors from layer-by-layer assembled SWNT films: importance of mechanical properties and a new figure of merit.

New transparent conductors (TCs) capable of replacing traditional indium tin oxide (ITO) are much needed for displays, sensors, solar cells, smart energy-saving windows, and flexible electronics. Technical requirements of TCs include not only high electrical conductivity and transparency but also environmental stability and mechanical property which are often overlooked in the research environment. Single-walled carbon nanotube (SWNT) coatings have been suggested as alternative TC materials but typically lack sufficient wear resistance compared to ITO. Balancing conductance, transparency, durability, and flexibility is a formidable challenge, which leads us to the introduction of a new TC figure of merit, PiTC, incorporating all these qualities. Maximization of PiTC to that of ITO or better can be suggested as an initial research goal. Fine tuning of SWNT layer-by-layer (LBL) polymeric nanocomposite structures makes possible integration of all the necessary properties. The produced TC demonstrated resistivity of 86 Omega/sq with 80.2% optical transmittance combined with tensile modulus, strength, and toughness of the film of 12.3+/-3.4 GPa, 218+/-13 MPa, and 8+/-1.7 J/g, respectively. A new transparent capping layer to conserve these properties in the hostile environment with matching or better strength, toughness, and transparency parameters was also demonstrated. Due to application demands, bending performance of TC made by LBL was of special interest and exceeded that of ITO by at least 100 times. Cumulative figure of merit PiTC for the produced coatings was 0.15 Omega(-1), whereas the conventional ITO showed PiTC<0.07 Omega(-1). With overall electrical and optical performance comparable to ITO and exceptional mechanical properties, the described coatings can provide an excellent alternative to ITO or other nanowire- and nanotube-based TC specifically in flexible electronics, displays, and sensors.

Layered carbon nanotube-polyelectrolyte electrodes outperform traditional neural interface materials.

The safety, function, and longevity of implantable neuroprosthetic and cardiostimulating electrodes depend heavily on the electrical properties of the electrode-tissue interface, which in many cases requires substantial improvement. While different variations of carbon nanotube materials have been shown to be suitable for neural excitation, it is critical to evaluate them versus other materials used for bioelectrical interfacing, which have not been done in any study performed so far despite strong interest to this area. In this study, we carried out this evaluation and found that composite multiwalled carbon nanotube-polyelectrolyte (MWNT-PE) multilayer electrodes substantially outperform in one way or the other state-of-the-art neural interface materials available today, namely activated electrochemically deposited iridium oxide (IrOx) and poly(3,4-ethylenedioxythiophene) (PEDOT). Our findings provide the concrete experimental proof to the much discussed possibility that carbon nanotube composites can serve as excellent new material for neural interfacing with a strong possibility to lead to a new generation of implantable electrodes.

Multiparameter structural optimization of single-walled carbon nanotube composites: toward record strength, stiffness, and toughness.

Efficient coupling of mechanical properties of SWNTs with the matrix leading to the transfer of unique mechanical properties of SWNTs to the macroscopic composites is a tremendous challenge of today's materials science. The typical mechanical properties of known SWNT composites, such as strength, stiffness, and toughness, are assessed in an introductory survey where we focused on concrete numerical parameters characterizing mechanical properties. Obtaining ideal stress transfer will require fine optimization of nanotube-polymer interface. SWNT nanocomposites were made here by layer-by-layer (LBL) assembly with poly(vinyl alcohol) (PVA), and the first example of optimization in respect to key parameters determining the connectivity at the graphene-polymer interface, namely, degree of SWNT oxidation and cross-linking chemistry, was demonstrated. The resulting SWNT-PVA composites demonstrated tensile strength (σ(ult)) = 504.5 ± 67.3 MPa, stiffness (E) = 15.6 ± 3.8 GPa, and toughness (K) = 121.2 ± 19.2 J/g with maximum values recorded at σ(ult) = 600.1 MPa, E = 20.6 GPa, and K = 152.1 J/g. This represents the strongest and stiffest nonfibrous SWNT composites made to date outperforming other bulk composites by 2-10 times. Its high performance is attributed to both high nanotube content and efficient stress transfer. The resulting LBL composite is also one of the toughest in this category of materials and exceeding the toughness of Kevlar by 3-fold. Our observation suggests that the strengthening and toughening mechanism originates from the synergistic combination of high degree of SWNT exfoliation, efficient SWNT-PVA binding, crack surface roughening, and fairly efficient distribution of local stress over the SWNT network. The need for a multiscale approach in designing SWNT composites is advocated.

Electrical stimulation of neural stem cells mediated by humanized carbon nanotube composite made with extracellular matrix protein.

One of the key challenges to engineering neural interfaces is to minimize their immune response toward implanted electrodes. One potential approach is to manufacture materials that bear greater structural resemblance to living tissues and by utilizing neural stem cells. The unique electrical and mechanical properties of carbon nanotubes make them excellent candidates for neural interfaces, but their adoption hinges on finding approaches for "humanizing" their composites. Here we demonstrated the fabrication of layer-by-layer assembled composites from single-walled carbon nanotubes (SWNTs) and laminin, which is an essential part of human extracellular matrix. Laminin-SWNT thin films were found to be conducive to neural stem cells (NSC) differentiation and suitable for their successful excitation. We observed extensive formation of functional neural network as indicated by the presence of synaptic connections. Calcium imaging of the NSCs revealed generation of action potentials upon the application of a lateral current through the SWNT substrate. These results indicate that the protein-SWNT composite can serve as materials foundation of neural electrodes with chemical structure better adapted with long-term integration with the neural tissue.

High-content screening as a universal tool for fingerprinting of cytotoxicity of nanoparticles.

Recent advances and progress in nanobiotechnology have demonstrated many nanoparticles (NPs) as potential and novel drug delivery vehicles, therapeutic agents, and contrast agents and luminescent biological labels for bioimaging. The emergence of new biomedical applications based on NPs signifies the need to understand, compare, and manage their cytotoxicity. In this study, we demonstrated the use of high-content screening assay (HCA) as a universal tool to probe the cytotoxicity of NPs and specifically cadmium telluride quantum dots (CdTe QDs) and gold NPs (Au NPs) in NG108-15 murine neuroblastoma cells and HepG2 human hepatocellular carcinoma cells. Neural cells represent special interest for NP-induced cytotoxicity because the optical and electrical functionalities of materials necessary for neural imaging and interfacing are matched well with the properties of many NPs. In addition, the cellular morphology of neurons is particularly suitable for automated high content screening. HepG2 cells represent a good model for high content screening studies since they are commonly used as a surrogate for human hepatocytes in pharmaceutical studies. We found the CdTe QDs to induce primarily apoptotic response in a time- and dosage-dependent manner and produce different toxicological profiles and responses in undifferentiated and differentiated neural cells. Au NPs were found to inhibit the proliferation and intracellular calcium release of HepG2 cells.

Successful differentiation of mouse neural stem cells on layer-by-layer assembled single-walled carbon nanotube composite.

The same properties that made carbon nanotube (CNT) composites interesting for electronics, sensing, and ultrastrong structural materials also make them an asset for biomedical engineering. The combination of electron conductivity, corrosion resistance, and strength are essential for neuroprosthetic devices. All of the studies in this area demonstrating cellular adhesion and signal transduction activity on CNT matrixes were conducted, so far, with terminally differentiated primary cells and cancerous cell lines. Neural stem cells are very plastic neural precursors capable of adapting to environmental conditions and recreating signal transduction pathways. Their intrinsic biological functionality not only makes the transition to stem cell cultures a difficult-to-avoid step but also implies several fundamentally important challenges. Here we demonstrate that mouse embryonic neural stem cells (NSCs) from the cortex can be successfully differentiated to neurons, astrocytes, and oligodendrocytes with clear formation of neurites on layer-by-layer (LBL) assembled single-walled carbon nanotube (SWNT)-polyelectrolyte multilayer thin films. Biocompatibility, neurite outgrowth, and expression of neural markers were similar to those differentiated on poly-L-ornithine (PLO), one of the most widely used growth substratums for neural stem cells.

Nanoscale engineering of a cellular interface with semiconductor nanoparticle films for photoelectric stimulation of neurons.

The remarkable optical and electrical properties of nanostructured materials are considered now as a source for a variety of biomaterials, biosensing, and cell interface applications. In this study, we report the first example of hybrid bionanodevice where absorption of light by thin films of quantum confined semiconductor nanoparticles of HgTe produced by the layer-by-layer assembly stimulate adherent neural cells via a sequence of photochemical and charge-transfer reactions. We also demonstrate an example of nanoscale engineering of the material driven by biological functionalities.

Lipid-gel and poly(dimethylsiloxane) film to mimic bioaccumulation in adipocytes.

Bioaccumulation is an increasingly important consideration in validation studies of the safety and efficacy of potential drugs. Although an "adipocyte" cell line model has been proven successful to mimic the accumulation of naphthalene in adipocytes, the prolonged incubation time limits its use in high-throughput studies and reduces reproducibility. In this investigation, naphthalene and naphthol accumulation and uptake kinetics of thin poly(dimethylsiloxane) (PDMS) film and lipid nanospheres suspended in a crosslinked gelatin gel (lipid-gel) were compared with those of adipocytes. Unlike the PDMS film, the lipid-gel can mimic the kinetics and extent of naphthalene accumulation in the adipocytes reasonably well. However, the lipid-gel accumulated about twice as much naphthol as the adipocytes, suggesting that hydrophobicity/hydrophilicity of the metabolite may be an important factor in the accuracy of accumulation studies with the lipid-gel. Nonetheless, the lipid-gel system shows promise as an inexpensive, convenient, and reproducible fat mimic for bioaccumulation studies.