Channels In Bilayers Research Articles

High-performance InOx/GaOx bilayer channel thin-film transistors made using persistent high-surface-energy induced by photochemical activation

In this paper, we report high-mobility InOx/GaOx bilayer channel thin-film transistors (TFTs) fabricated using the persistent high-surface-energy characteristic of photochemically activated metal-oxide films. The photochemically-activated metal-oxide films exhibited persistent high surface-energy characteristics compared to a thermally annealed film, which enabled the facile vertical stacking of oxide films using a solution-based process. By using the photochemical activation process as an annealing method and by employing an InOx/GaOx bilayer channel structure, high-mobility oxide TFTs with saturation field-effect mobilities as high as 15.7 cm2/V-s were obtained with an average value of 11.2 ± 1.9 cm2/V-s. Various spectroscopic and surface analyses were performed to elucidate the persistent high surface-energy behavior and the dynamic changes in surface states.

Interfacial Charge Engineering in Ferroelectric-Controlled Mott Transistors.

Heteroepitaxial coupling at complex oxide interfaces presents a powerful tool for engineering the charge degree of freedom in strongly correlated materials, which can be utilized to achieve tailored functionalities that are inaccessible in the bulk form. Here, the charge-transfer effect between two strongly correlated oxides, Sm0.5 Nd0.5 NiO3 (SNNO) and La0.67 Sr0.33 MnO3 (LSMO), is exploited to realize a giant enhancement of the ferroelectric field effect in a prototype Mott field-effect transistor. By switching the polarization field of a ferroelectric Pb(Zr,Ti)O3 (PZT) gate, nonvolatile resistance modulation in the Mott transistors with single-layer SNNO and bilayer SNNO/LSMO channels is induced. For the same channel thickness, the bilayer channels exhibit up to two orders of magnitude higher resistance-switching ratio at 300 K, which is attributed to the intricate interplay between the charge screening at the PZT/SNNO interface and the charge transfer at the SNNO/LSMO interface. X-ray absorption spectroscopy and X-ray photoelectron spectroscopy studies of SNNO/LSMO heterostructures reveal about 0.1 electron per 2D unit cell transferred between the interfacial Mn and Ni layers, which is corroborated by first-principles density functional theory calculations. The study points to an effective strategy to design functional complex oxide interfaces for developing high-performance nanoelectronic and spintronic applications.

Island‐Like AZO/Al2O3 Bilayer Channel Structure for Thin Film Transistors

Aluminum‐doped zinc oxide (AZO) has been regarded as a potential and promising material for thin‐film transistors (TFTs) owing to its low cost and nontoxicity. Generally, the high conductivity of AZO should be suitably reduced before using in TFTs as a semiconductor. Traditional ways to reduce the conductivity of AZO is by increasing doping content of aluminum (>5 at%). Herein, a novel approach is first reported to convert conductive AZO into a semiconductor by rationally designing a bilayer channel structure that consists of an AZO island film and a thin Al2O3 film, serving as “electron donor” and “electron bridge,” respectively. Consequently, TFTs with island‐like AZO/Al2O3 channel material present the saturation mobility of 8.04 cm2 V−1 s−1, on/off current of 1.6 × 107, and subthreshold swing of 0.83 V dec−1. Moreover, the underlying mechanism for the excellent electrical properties of obtained TFTs is that the electron conduction in AZO/Al2O3‐TFTs is proved to be dominated by the percolation conduction due to the effective control of carriers concentration. This method proposed in this report sheds light on the conversion of conductive oxide film to semiconductor layer for TFTs.

Thin-Film Transistors With Amorphous Indium–Gallium-Oxide Bilayer Channel

The authors report the deposition of amorphous indium–gallium-oxide (a-IGO) films on glass substrate by co-sputtering and the fabrication of thin film transistors (TFTs) with a-IGO bilayer channel. It was found that the electron mobility, $\mu _\text{FE}$ , sub-threshold swing, SS, and $\text{I}_{\text {on}}/\text{I}_{\text {off}}$ ratio of the fabricated TFTs were all better than those reported previously from the TFTs with single a-IGO channel. By properly controlling the sputtering powers, we achieved TFTs with $\mu _{\text {FE}}$ of 53.2 cm 2/Vs, SS of 0.19 V/decade and $\text{I}_{\text {on}}/\text{I}_{\text {off}}$ ratio of ~107.

Assessment of Endogenous and Exogenous Modulators of the TRPM7 Channel in Planar Lipid Bilayers

TRPM7 is ubiquitously expressed divalent cation-selective ion channel. The channel subunit contains the alpha-kinase domain, which is located at the C-terminus. TRPM7 channels are implicated in a variety of cellular processes, including cell proliferation, differentiation, survival, death, Mg2+ homeostasis, and oxidative stress. TRPM7 is essential for the early embryonic development as the knockout of its gene results in embryonic lethality of mice. Furthermore, TRPM7 plays important roles in thymopoiesis, kidney morphogenesis, cardiac rhythmicity and immune responses.

Identification of Novel and Natural High Affinity Peptide Inhibitors of KcsA by Phage-Display Reveals an Unexpected Mechanism of Pore Blockade

Peptide neurotoxins are powerful tools for research, diagnosis and treatment of disease. Limiting broader use, most receptors lack an identified toxin that binds with high-affinity and specificity. Here we describe isolation of toxins for one such orphan target, KcsA, a K+ channel that has been fundamental to delineating the structural basis for ion channel function. A phage display strategy is employed whereby ∼1.5 million novel and natural peptides are fabricated on the scaffold present in ShK, a sea anemone type I (SAK1) toxin stabilized by three disulfide bonds. We focus here on two of nine toxins selected by sorting on purified KcsA, one novel (Hui1, 34 residues) and one natural (HmK, 35 residues). Hui1 is potent, blocking single KcsA channels in planar lipid bilayers half-maximally (Ki) at 1 nM. Hui1 is also specific, inhibiting KcsA-Shaker channels in Xenopus oocytes with a Ki of 0.5 nM while Shaker, Kv1.2 and Kv1.3 channels are blocked over 200-fold less well. In contrast, HmK is potent but promiscuous, blocking KcsA-Shaker, Shaker, Kv1.2 and Kv1.3 channels with Ki of 1 to 4 nM. As anticipated, one Hui1 blocks the KcsA pore and two conserved toxin residues, Lys21 and Tyr22, are essential for high affinity binding. Unexpectedly, K+ ions traversing the channel from the inside confer voltage-sensitivity to the Hui1 off-rate via Arg23, indicating that Lys21 is not in the pore. The 3D structure of Hui1 reveals a SAK1 fold, rationalizes KcsA inhibition, and validates the scaffold-based approach for isolation of high-affinity toxins for orphan receptors.

Strain and deformations engineered germanene bilayer double gate-field effect transistor by first principles

Germanene, silicene, stanene, phosphorene and graphene are some of single atomic materials with novel properties. In this paper, we explored bilayer germanene-based Double Gate-Field Effect Transistor (DG-FET) with various strains and deformations using Density Functional Theory (DFT) and Green’s approach by first-principle calculations. The DG-FET of 1.6nm width, 6nm channel length (Lch) and HfO2 as gate dielectric has been modeled. For intrinsic deformation of germanene bilayer, we have enforced minute mechanical deformation of wrap and twist (5°) and ripple (0.5Å) on germanene bilayer channel material. By using NEGF formalism, I–V Characteristics of various strains and deformation tailored DG-FET was calculated. Our results show that rough edge and single vacancy (5–9) in bilayer germanene diminishes the current around 47% and 58% respectively as compared with pristine bilayer germanene. In case of strain tailored bilayer DG-FET, multiple NDR regions were observed which can be utilized in building stable multiple logic states in digital circuits and high frequency oscillators using negative resistive techniques.

Probing Conformational Changes during the Gating Cycle of a Potassium Channel in Lipid Bilayers

Ion conduction across the cellular membrane requires the simultaneous opening of activation and inactivation gates of the K+ channel pore. The bacterial KcsA channel has served as a powerful system for dissecting the structural changes that are related to four major functional states associated with K+ gating. Yet, the direct observation of the full gating cycle of KcsA has remained structurally elusive, and crystal structures mimicking these gating events require mutations in or stabilization of functionally relevant channel segments. Here, we found that changes in lipid composition strongly increased the KcsA open probability. This enabled us to probe all four major gating states in native-like membranes by combining electrophysiological and solid-state NMR experiments. In contrast to previous crystallographic views, we found that the selectivity filter and turret region, coupled to the surrounding bilayer, were actively involved in channel gating. The increase in overall steady-state open probability was accompanied by a reduction in activation-gate opening, underscoring the important role of the surrounding lipid bilayer in the delicate conformational coupling of the inactivation and activation gates.

All-sputtered, flexible, bottom-gate IGZO/Al2O3 bi-layer thin film transistors on PEN fabricated by a fully room temperature process

In this work, an innovative all-sputtered bottom-gate thin film transistor (TFT) using an amorphous InGaZnO (IGZO)/Al2O3 bi-layer channel was fabricated by fully room temperature processes on a flexible PEN substrate.

The multiple assemblies of VDAC: from conformational heterogeneity to β-aggregation and amyloid formation.

From their cellular localisation, to their atomic structure and their involvement in mitochondrial-driven cell death, voltage-dependent anion channels (VDACs) have challenged the scientific community with enigmas and paradoxes for over four decades. VDACs form active monomer channels in lipid bilayers, but they can also organise in multimeric assemblies. What induces, regulates and/or controls the monomer-multimer dynamics at the cellular level is not known. However, these state transitions appear to be relevant for mitochondria in making life or death decisions and for driving developmental processes. This review starts with a general introduction on VDACs and continues by examining VDAC oligomerisation/aggregation in light of recent discussions on VDAC-β-amyloid interactions and their involvement in Alzheimer's disease.

Circulation Research “In This Issue” Anthology

Circulation Research “In This Issue” Anthology

Boost up the electrical performance of InGaZnO thin film transistors by inserting an ultrathin InGaZnO:H layer

This study examined the electrical performance of bilayer channel InGaZnO:H/InGaZnO thin-film transistors (TFTs). The field-effect mobility and bias stress stability of the InGaZnO device were improved by inserting the hydrogenated InGaZnO ultrathin layer compared to the pure InGaZnO single channel layer device. As a consequence, a high field-effect mobility of 55.3 cm2/V s, a high on/off current ratio of 108, a threshold voltage of 0.7 V, and a small sub-threshold swing of 0.18 V/decade have been achieved. The X-ray photoelectron spectroscopy and low-frequency noise analysis suggest that these desirable properties should be attributed to the ultrathin InGaZnO:H layer, which could provide suitable carrier concentration and reduce the average trap density near the channel and insulator layer interface. Meanwhile, the channel conductance of the bilayer device is controlled by thick InGaZnO layer through formation barrier energy for electron transport at the interface of InGaZnO:H and InGaZnO layer. These improved electrical properties have represented a great step towards the achievement of transparent, high performances, and low-cost metal oxide TFTs.

Cholesterol influences potassium currents in inner hair cells isolated from guinea pig cochlea.

There is a correlation between serum hyperlipidemia and hearing loss. Cholesterol is an integral component of the cell membrane and regulates the activity of ion channels in the lipid bilayer. The aim of this study was to investigate the effects of cholesterol on the potassium currents in IHCs by using the cholesterol-depleting drug, MβCD, and water-soluble cholesterol. IHCs were acutely isolated from a mature guinea-pig cochlea and potassium currents were recorded. MβCD and water-soluble cholesterol were applied to IHCs under pressure puff pipettes. IHCs showed outwardly rectifying currents (IK,f and IK,s) in response to depolarizing voltage pulses, with only a slight inward current (IK,n) when hyperpolarized. In 10mM MβCD solutions, the amplitude of outward K currents reversely decreased; however, fast activation kinetics was preserved. In contrast, in solution of 1mM water-soluble cholesterol, the amplitude of outward K currents reversely increased. At the membrane potential of +110mV, relative conductances were 0.87±0.07 and 1.18±0.11 in MβCD solutions and cholesterol solutions, respectively. The amplitude of K currents in isolated IHCs was reversely changed by cholesterol-depleting drug and water-soluble cholesterol. These results demonstrated the possibility of the involvement of IHC function in hyperlipidemia-induced inner ear disorders.

1-V Full-Swing Depletion-Load a-In–Ga–Zn–O Inverters for Back-End-of-Line Compatible 3D Integration

To enable monolithic three-dimensional integration of the amorphous In–Ga–Zn–O (a-IGZO) and CMOS technologies, the a-IGZO inverters compatible with the low operating voltage ( $\leqq 1$ V) and process temperature of back-end-of-line CMOS have been investigated. We demonstrated a full-swing depletion-load inverter with a voltage gain up to 24 using a CMOS-compatible operating voltage of 1 V. The drive transistor was realized using a low-voltage enhancement-mode a-IGZO thin-film transistor (TFT) with a steep subthreshold swing of 70 mV/decade and a low threshold voltage of 0.5 V. The load transistor was implemented using a bi-layer a-IGZO channel, where the a-IGZO composition was modulated simply by the oxygen flow rate in a depletion-mode TFT.

Quasi Two-Dimensional Dye-Sensitized In2O3 Phototransistors for Ultrahigh Responsivity and Photosensitivity Photodetector Applications.

We report the development of dye-sensitized thin-film phototransistors consisting of an ultrathin layer (<10 nm) of indium oxide (In2O3) the surface of which is functionalized with a self-assembled monolayer of the light absorbing organic dye D102. The resulting transistors exhibit a preferential color photoresponse centered in the wavelength region of ∼500 nm with a maximum photosensitivity of ∼10(6) and a responsivity value of up to 2 × 10(3) A/W. The high photoresponse is attributed to internal signal gain and more precisely to charge carriers generated upon photoexcitation of the D102 dye which lead to the generation of free electrons in the semiconducting layer and to the high photoresponse measured. Due to the small amount of absorption of visible photons, the hybrid In2O3/D102 bilayer channel appears transparent with an average optical transmission of >92% in the wavelength range 400-700 nm. Importantly, the phototransistors are processed from solution-phase at temperatures below 200 °C hence making the technology compatible with inexpensive and temperature sensitive flexible substrate materials such as plastic.

TRPM3 Exhibits Slight Temperature Sensitivity in the Planar Lipid Bilayer System and Requires the Presence of PIP2

Transient Receptor Potential Melastatin 3 (TRPM3) channel is critical for various physiological processes. In sensory nervous system TRPM3 has been implicated in temperature perception and inflammatory hyperalgesia, while in pancreatic β-cells the channel was linked to glucose-induced insulin release. In cells, TRPM3 is activated by heat and chemical agonists, including neurosteroid, pregnenolone sulfate (PS), and L-type Ca2+ channel blocker, nifedipine. To define the physical interactions and nuances of TRPM3 channel activity with its modulators, we succeeded to incorporate purified TRPM3 protein into the artificial membrane system - planar lipid bilayers. We found that channel opening by PS required the presence of phosphatidylinositol-4,5-bisphosphate (PIP2) or clotrimazole. In the presence of 5 μM PIP2 the channel exhibited EC50 for PS of ∼1.3 μM, which is lower than that observed in cell recordings (∼23 μM), due to higher agonist's sensitivity of the channel in bilayers. Unlike PS, the presence of nifedipine alone sufficed to induce TRPM3 activity (EC50 = ∼1.7 μM), in which case channel demonstrated distinct gating behavior. Similarly to PS, EC50 of TRPM3 to nifedipine in cell recordings was much higher (∼32 μM), than that observed in the bilayers.We also performed an extensive thermodynamic analysis on TRPM3 temperature dependence. Intriguingly, we found that TRPM3 exhibits slight temperature sensitivity in comparison to highly temperature-sensitive TRPM8 or TRPV1. TRPM3 remained closed upon heat-induced stimuli, but exhibited openings in the presence of PIP2 (Q10 = 5.3), although only with low open probability profile (Po = 0.048 ± 0.016).Together our results resolved the details on TRPM3 channel function in isolated system, which confirmed its direct gating by PS and PIP2, but indicated lack of strong intrinsic temperature sensitivity, common to other thermo-sensitive TRP channels.

Probing Single-Molecule Ion Channel Conformational Dynamics in Living Cells

Stochastic and inhomogeneous conformational changes regulate the function and dynamics of ion channels that are crucial for cell functions, neuronal signaling, and brain functions. We have developed a new combined approaches of using single ion channel patch-clamp electrical recording and single-molecule fluorescence imaging for probing ion channel conformational changes simultaneously with the electrical single channel recording. By combining real-time single-molecule fluorescence imaging measurements with real-time single-channel electric current measurements in artificail lipid bilayers and in living cell membranes, we were able to probe single ion-channel-protein conformational changes simultaneously, and thus providing an understanding the dynamics and mechanism of ion-channel proteins at the molecular level. We will focus our discussion on the new development and results of real-time imaging of the dynamics of gramicidin, colicin, and NMDA receptor ion channels in lipid bilayers and living cells. We have probed NMDA (N-Methyl-D-Aspartate) receptor ion channel in live HEK-293 cell, especially, the single ion channel open-close activity and its associated protein conformational changes simultaneously. Furthermore, we have revealed that the seemingly identical electrically off states are associated with multiple conformational states. Based on our experimental results, we have proposed a multistate clamshell model to interpret the NMDA receptor open-close dynamics. Our results shed light on new perspectives of the intrinsic interplay of lipid membrane dynamics, solvation dynamics, and the ion channel functions.

Testosterone is a Highly Potent and Specific Agonist of TRPM8

The role of the TRPM8 channel in the peripheral nervous system as a major receptor for cold temperatures has been well established. Less certainty was gained about the role of the channel beyond the nervous system. Particularly, the presence and high expression levels of TRPM8 in the prostate epithelium were not well understood. Recently, we identified that the prevalent male hormone, testosterone, is a highly potent endogenous agonist of TRPM8 channels. Picomolar concentrations of testosterone elicited rapid Ca2+-uptake in cells expressing TRPM8, including prostate epithelial cells and neurons. Furthermore, testosterone evoked openings of the purified TRPM8 channel in planar lipid bilayers that were promptly inhibited with TRPM8 antagonists, or the purified androgen receptor (AR) protein. In the bilayers, TRPM8 activity was induced by both, permeable testosterone, as well as an impermeable analog, testosterone covalently conjugated to BSA. Interestingly, BSA-testosterone evoked openings of TRPM8 only into a small conductance state, with a mean slope conductance of ∼7 pS, in comparison to ∼37 pS obtained with the permeable analog. Furthermore, the prevalent female hormones, estradiol and progesterone, had no effect on the channel at picomolar or nanomolar concentrations, and only exerted openings at micromolar concentrations, but even then these steroids could open TRPM8 only into a small conductance state of ∼8 pS. These results indicate that binding of steroids to the extracellular site induces conformational changes of the channel resulting in a narrow permeation path. Together, our results demonstrate that testosterone is not only a highly potent but also a highly specific agonist of TRPM8.

Two types of syringomycin E channels in sphingomyelin-containing bilayers.

The influence of dipole modifiers on the characteristics of single syringomycin E (SRE) channels in bilayers comprising DOPS, DOPE, sphingolipids (sphingomyelin, N-stearoyl-phytosphingosine or N-stearoyl-sphinganine) and sterols (cholesterol or ergosterol) was studied. The effects of dipole modifiers on SRE channel amplitudes were dependent upon the sphingolipid type and were not affected by the membrane sterol content. A decrease in the dipole potential of phytosphingosine- and sphinganine-containing bilayers, which was induced by the adsorption of phloretin, led to a reduction in conductance; however, an increase in this potential, which occurred upon the addition of RH 421, led to an enhancement in the conductance of SRE channels. Two channel populations, one of which is sensitive while the other is insensitive to modifiers, were found in sphingomyelin-containing bilayers. This indicates that SRE channels are distributed in lipid domains with different dipole potentials.

Stimulation-dependent gating of TRPM3 channel in planar lipid bilayers.

The transient receptor potential melastatin (TRPM)-3 channel is critical for various physiologic processes. In somatosensory neurons, TRPM3 has been implicated in temperature perception and inflammatory hyperalgesia, whereas in pancreatic β-cells the channel has been linked to glucose-induced insulin release. As a typical representative of the TRP family, TRPM3 is highly polymodal. In cells, it is activated by heat and chemical agonists, including pregnenolone sulfate (PS) and nifedipine (Nif). To define the nuances of TRPM3 channel activity and its modulators, we succeeded in incorporating the TRPM3 protein into planar lipid bilayers. We found that phosphatidylinositol-4,5-bisphosphate (PIP2) or clotrimazole is necessary for channel opening by PS. Unlike PS, the presence of Nif alone sufficed to induce TRPM3 activity and demonstrated distinct gating behavior. We also performed an extensive thermodynamic analysis of TRPM3 activation and found that TRPM3 exhibited slight temperature sensitivity in the bilayers. In the absence of other agonists TRPM3 channels remained closed upon heat-induced stimulation, but opened in the presence of PIP2, although with only a low open-probability profile. Together, our results elucidate the details peculiar to TRPM3 channel function in an isolated system. We confirmed its direct gating by PS and PIP2, but found a lack of the strong intrinsic temperature sensitivity common to other thermosensitive TRP channels.