Local Disordering in the Amorphous Network of a Solution-Processed Indium Tin Oxide Thin Film.

The polyhedra unit structure (MOx) in an amorphous metal oxide network has more freedom and flexibility than the same unit structure in a crystalline phase. Consequently, a mild external stimulus (e.g., instant photonic and acoustic energy) could affect and change this network parameter, thereby enhancing and modulating the electrical properties. However, it is difficult to tune these atomic parameters solely while maintaining the metal oxide's initial global amorphous phase and thereby preventing mechanical instability at the film-substrate interface (i.e., cracking or distortion). Here, we report local disordering in an amorphous network of a solution-processable indium tin oxide (ITO) film, where the disordering is triggered by mild-light irradiation (<0.1 mJ/cm2). Through a combination of systematic characterizations of the global structural and chemical compositional changes in conjunction with extended X-ray absorption fine structure analyses, we revealed the distortion of the atomic structure in the amorphous network of the ITO film led to the formation of additional structural oxygen vacancies. Our findings enabled us to fabricate mechanical-instability-free, perfect amorphous-phase ITO thin films on plastic substrates, where the sheet resistance substantially decreased to ∼ 2 × 103 Ω/□. Furthermore, this sheet resistance did not vary when the film and substrate were bent to a radius of 2 mm and could operate at low temperatures. This work can pave the novel way to fabricate high-quality flexible transparent electrodes suitable for rapid, cost-effective, and patternable processing on plastic substrates, and the domain can be extended to flexible electronics.

Multilayer fabrication of unobtrusive poly(dimethylsiloxane) nanobrush for tunable cell adhesion.

Precise modulation of polymer brush in its thickness and grafting density can cause unexpected cell behaviors and regulated bioactivities. Herein, a nanoscale poly(dimethylsiloxane) (PDMS) brush was employed to use as a controllable material for cell adhesion. Facile fabrication of ultrathin monolayer PDMS nanobrush on an underlying substrate facilitated regaining cell adhesion through long-range cell attractive forces such as the van der Waals forces. We showed that cell adhesion is diminished by increasing the number of nanobrush layers, causing a gradual decrease of the effectiveness of the long-range force. The result demonstrates that ultrathin PDMS nanobrush can either promote or inhibit cell adhesion, which is required for various biomedical fields such as tissue-engineering, anti-fouling coating, and implantable biomaterials and sensors.

Polymer brush: a promising grafting approach to scaffolds for tissue engineering.

Polymer brush is a soft material unit tethered covalently on the surface of scaffolds. It can induce functional and structural modification of a substrate's properties. Such surface coating approach has attracted special attentions in the fields of stem cell biology, tissue engineering, and regenerative medicine due to facile fabrication, usability of various polymers, extracellular matrix (ECM)-like structural features, and in vivo stability. Here, we summarized polymer brush-based grafting approaches comparing self-assembled monolayer (SAM)-based coating method, in addition to physico-chemical characterization techniques for surfaces such as wettability, stiffness/ elasticity, roughness, and chemical composition that can affect cell adhesion, differentiation, and proliferation. We also reviewed recent advancements in cell biological applications of polymer brushes by focusing on stem cell differentiation and 3D supports/implants for tissue formation. Understanding cell behaviors on polymer brushes in the scale of nanometer length can contribute to systematic understandings of cellular responses at the interface of polymers and scaffolds and their simultaneous effects on cell behaviors for promising platform designs. [BMB Reports 2016; 49(12): 655-661].

Micropillar arrays as potential drug screens: Inhibition of micropillar-mediated activation of the FAK-Src-paxillin signaling pathway by the CK2 inhibitor CX-4945.

Here, we demonstrate the possible applications of micropillar arrays in screening anti-metastasis drugs. Human lung adenocarcinoma A549 cells incubated in multiwell plates containing micropillars exhibited markedly different physical/biochemical behavior depending on pillar dimensions. In particular, A549 cells grown in plates containing 2-µm diameter, 16-µm pitched pillar arrays showed epithelial-to-mesenchymal transition (EMT)-like behavior; cell body elongation, and highly increased activation of the focal adhesion kinase (FAK)-Src-paxillin signaling cascade. FAK is the most prominent kinase involved in dynamic regulation of the actin cytoskeleton and cell adhesion, migration, and invasion. Activation of FAK, a hallmark of cancer cell adhesion and migration, is normally induced by various growth factors, such as transforming growth factor-ß (TGF-ß). Here, we found that pillar-mediated activation of signaling molecules mimicked that induced by TGF-ß. Notably, micropillar arrays with specific dimensions accelerated the elongation of cells, an effect linked to the activation of signaling molecules related to EMT. Micropillar-induced FAK activation could be arrested by the casein kinase-2 (CK2) inhibitor CX-4945, a drug candidate with activity against TGF-ß-induced cancer cell metastasis, demonstrating the possibility of using inorganic microstructures for cell-based drug screening. STATEMENT OF SIGNIFICANCE: In this work, we have fabricated flexible substrates with regular arrays of micrometersized pillars, and used them to grow A549 human lung adenocarcinoma cells. Cells exhibit dramatically different behavior depending on the intervals of pillars. Especially, cells grown in certain pillar structures show epithelial-to mesenchmal transition (EMT)-like morphology and related molecules, which is similar to the activation obtained using expensive cytokine TGF-ß. Based on the fact that pillar arrays may activate EMT like transition, screening of anti-cancer drug using pillar arrays have demonstrated as well in our work. Our study confirms that mechanical stimulation may exert similar effects with chemical stimulation, and such mechanical structures could be used as a large-scale drug screening platforms. Cell morphogenesis on engineered substrate is not new, but the present work could be distinguished with its unique fabrication process that can mass produce the structures and it could be applied for high-throughput drug screening. Also, we suggest the formation of focal adhesions on pillar structures and consequent strain as the possible mechanism behind the observed EMT-like transition. Currently, we are working on full-scale profiling of metabolomics and proteomics of cells grown in large-scale pillar arrays as well.

Performance assessments of vertically aligned carbon nanotubes multi-electrode arrays using Cath.a-differentiated (CAD) cells.

In this work, Cath.a-differentiated (CAD) cells were used in place of primary neuronal cells to assess the performance of vertically aligned carbon nanotubes (VACNTs) multi-electrode arrays (MEA). To fabricate high-performance MEA, VACNTs were directly grown on graphene/Pt electrodes via plasma enhanced chemical deposition technique. Here, graphene served as an intermediate layer lowering contact resistance between VACNTs and Pt electrode. In order to lower the electrode impedance and to enhance the cell adhesion, VACNTs-MEAs were treated with UV-ozone for 20 min. Impedance of VACNTs electrode at 1 kHz frequency exhibits a reasonable value (110 kΩ) for extracellular signal recording, and the signal to noise ratio the is good enough to measure low signal amplitude (15.7). Spontaneous firing events from CAD cells were successfully measured with VACNTs MEAs that were also found to be surprisingly robust toward the biological interactions.

Effects of substrate conductivity on cell morphogenesis and proliferation using tailored, atomic layer deposition-grown ZnO thin films.

We demonstrate that ZnO films grown by atomic layer deposition (ALD) can be employed as a substrate to explore the effects of electrical conductivity on cell adhesion, proliferation, and morphogenesis. ZnO substrates with precisely tunable electrical conductivity were fabricated on glass substrates using ALD deposition. The electrical conductivity of the film increased linearly with increasing duration of the ZnO deposition cycle (thickness), whereas other physical characteristics, such as surface energy and roughness, tended to saturate at a certain value. Differences in conductivity dramatically affected the behavior of SF295 glioblastoma cells grown on ZnO films, with high conductivity (thick) ZnO films causing growth arrest and producing SF295 cell morphologies distinct from those cultured on insulating substrates. Based on simple electrostatic calculations, we propose that cells grown on highly conductive substrates may strongly adhere to the substrate without focal-adhesion complex formation, owing to the enhanced electrostatic interaction between cells and the substrate. Thus, the inactivation of focal adhesions leads to cell proliferation arrest. Taken together, the work presented here confirms that substrates with high conductivity disturb the cell-substrate interaction, producing cascading effects on cellular morphogenesis and disrupting proliferation, and suggests that ALD-grown ZnO offers a single-variable method for uniquely tailoring conductivity.

Europium-doped gadolinium sulfide nanoparticles as a dual-mode imaging agent for T1-weighted MR and photoluminescence imaging.

We present a facile synthesis of europium-doped gadolinium sulfide (GdS:Eu(3+)) opto-magnetic nanoparticles (NPs) via sonochemistry. Their photoluminescence and strong paramagnetic properties enable these NPs to be utilized as an in vitro cell imaging and in vivo T(1)-weighted MR imaging probe. The GdS:Eu(3+) NPs have a prominent longitudinal (r(1)) relaxivity value, which is a critical parameter for T(1)-weighted MR imaging. Here, we showed not only their strong positive contrast effect to blood vessels and organs of mice, but also blood half-life and biodistribution including clearance from organs, in order to assess the GdS:Eu(3+) NPs as a competent nanocrystal-based T(1) contrast agent. We further showed confocal images of breast cancer cells containing GdS:Eu(3+) NPs to evaluate as a photoluminescence probe. Dual-mode imaging capability obtained from the GdS:Eu(3+) NPs will allow target-oriented cellular imaging as well as the resulting disease-specific MR imaging.

A facile reduction of Eu3+ to Eu2+ in gadolinium monosulfide nanoparticles using a mixed solvent of oleic acid/hexadecylamine.

We prepared GdS:Eu(3+) by simple thermal decomposition under 1-dodecanethiol. A reduction process was observed from Eu(3+) to Eu(2+) when oleic acid and hexadecylamine were injected into GdS:Eu(3+). Under UV excitation, GdS:Eu(3+) showed an intense orange-red emission and GdS:Eu(2+) showed a broad green band.