MspA Porin as a Local Nanopore Probe for Membrane-bound Proteins

Nanopore sensing is based on detection and analysis of nanopore transient conductance changes induced by analyte capture. We have recently shown that α-Synuclein (αSyn), an intrinsically disordered, membrane-active, neuronal protein implicated in Parkinson disease, can be reversibly captured by the VDAC nanopore. The capture process is a highly voltage dependent complexation of the two proteins where transmembrane potential drives the polyanionic C-terminal domain of αSyn into VDAC--exactly the mechanism by which generic nanopore-based interrogation of proteins and polynucleotides proceeds. The complex formation, and the motion of αSyn in the nanopore, thus may be expected to be only indirectly dependent on the pore identity. Here, we confirm this prediction by demonstrating that when VDAC is replaced with a different transmembrane pore, the engineered mycobacterial porin M2MspA, all the qualitative features of the αSyn/nanopore interaction are preserved. The rate of αSyn capture by M2MspA rises exponentially with the applied field, while the residence time displays a crossover behavior, indicating that at voltages >50 mV M2MspA-bound αSyn largely undergoes translocation to the other side of the membrane. The translocation is directly confirmed using the selectivity tag method, in which the polyanionic C-terminal and neutral N-terminal regions of αSyn alter the selectivity of the M2MspA channel differently, allowing direct discrimination of translocation vs retraction for single αSyn molecules. We thus prove that the physical model of the motion of disordered protein chains in the nanopore confinement and the selectivity tag technique are not limited to VDAC but are broadly applicable to nanopore-based protein detection, analysis, and separation technologies.

A Comparison of Regional Classification Strategies Implemented for the Population Based Approach to Modelling Atrial Fibrillation

(1) Background: in silico models are increasingly relied upon to study the mechanisms of atrial fibrillation. Due to the complexity associated with atrial models, cellular variability is often ignored. Recent studies have shown that cellular variability may have a larger impact on electrophysiological behaviour than previously expected. This paper compares two methods for AF remodelling using regional populations. (2) Methods: using 200,000 action potentials, experimental data was used to calibrate healthy atrial regional populations with two cellular models. AF remodelling was applied by directly adjusting maximum channel conductances. AF remodelling was also applied through adjusting biomarkers. The methods were compared upon replication of experimental data. (3) Results: compared to the percentage method, the biomarker approach resulted in smaller changes. RMP, APD20, APD50, and APD90 were changed in the percentage method by up to 11%, 500%, 50%, and 60%, respectively. In the biomarker approach, RMP, APD20, APD50, and APD90 were changed by up to 4.5%, 132%, 50%, and 35%, respectively. (4) Conclusion: applying AF remodelling through biomarker-based clustering resulted in channel conductance changes that were consistent with experimental data, while maintaining the highly non-linear relationships between channel conductances and biomarkers. Directly changing conductances in the healthy regional populations impacted the non-linear relationships and resulted in non-physiological APD20 and APD50 values.

Giant conductivity of mobile non-oxide domain walls

Atomically sharp domain walls in ferroelectrics are considered as an ideal platform to realize easy-to-reconfigure nanoelectronic building blocks, created, manipulated and erased by external fields. However, conductive domain walls have been exclusively observed in oxides, where domain wall mobility and conductivity is largely influenced by stoichiometry and defects. Here, we report on giant conductivity of domain walls in the non-oxide ferroelectric GaV4S8. We observe conductive domain walls forming in zig-zagging structures, that are composed of head-to-head and tail-to-tail domain wall segments alternating on the nanoscale. Remarkably, both types of segments possess high conductivity, unimaginable in oxide ferroelectrics. These effectively 2D domain walls, dominating the 3D conductance, can be mobilized by magnetic fields, triggering abrupt conductance changes as large as eight orders of magnitude. These unique properties demonstrate that non-oxide ferroelectrics can be the source of novel phenomena beyond the realm of oxide electronics.

Low-energy room-temperature optical switching in mixed-dimensionality nanoscale perovskite heterojunctions

Long-lived photon-stimulated conductance changes in solid-state materials can enable optical memory and brain-inspired neuromorphic information processing. It remains challenging to realize optical switching with low-energy consumption, and new mechanisms and design principles giving rise to persistent photoconductivity (PPC) can help overcome an important technological hurdle. Here, we demonstrate versatile heterojunctions between metal-halide perovskite nanocrystals and semiconducting single-walled carbon nanotubes that enable room-temperature, long-lived (thousands of seconds), writable, and erasable PPC. Optical switching and basic neuromorphic functions can be stimulated at low operating voltages with femto- to pico-joule energies per spiking event, and detailed analysis demonstrates that PPC in this nanoscale interface arises from field-assisted control of ion migration within the nanocrystal array. Contactless optical measurements also suggest these systems as potential candidates for photonic synapses that are stimulated and read in the optical domain. The tunability of PPC shown here holds promise for neuromorphic computing and other technologies that use optical memory.

Stomatal conductance limited the CO2 response of grassland in the last century

Background The anthropogenic increase of atmospheric CO2 concentration (ca) is impacting carbon (C), water, and nitrogen (N) cycles in grassland and other terrestrial biomes. Plant canopy stomatal conductance is a key player in these coupled cycles: it is a physiological control of vegetation water use efficiency (the ratio of C gain by photosynthesis to water loss by transpiration), and it responds to photosynthetic activity, which is influenced by vegetation N status. It is unknown if the ca-increase and climate change over the last century have already affected canopy stomatal conductance and its links with C and N processes in grassland. Results Here, we assessed two independent proxies of (growing season-integrating canopy-scale) stomatal conductance changes over the last century: trends of δ18O in cellulose (δ18Ocellulose) in archived herbage from a wide range of grassland communities on the Park Grass Experiment at Rothamsted (U.K.) and changes of the ratio of yields to the CO2 concentration gradient between the atmosphere and the leaf internal gas space (ca – ci). The two proxies correlated closely (R2 = 0.70), in agreement with the hypothesis. In addition, the sensitivity of δ18Ocellulose changes to estimated stomatal conductance changes agreed broadly with published sensitivities across a range of contemporary field and controlled environment studies, further supporting the utility of δ18Ocellulose changes for historical reconstruction of stomatal conductance changes at Park Grass. Trends of δ18Ocellulose differed strongly between plots and indicated much greater reductions of stomatal conductance in grass-rich than dicot-rich communities. Reductions of stomatal conductance were connected with reductions of yield trends, nitrogen acquisition, and nitrogen nutrition index. Although all plots were nitrogen-limited or phosphorus- and nitrogen-co-limited to different degrees, long-term reductions of stomatal conductance were largely independent of fertilizer regimes and soil pH, except for nitrogen fertilizer supply which promoted the abundance of grasses. Conclusions Our data indicate that some types of temperate grassland may have attained saturation of C sink activity more than one century ago. Increasing N fertilizer supply may not be an effective climate change mitigation strategy in many grasslands, as it promotes the expansion of grasses at the disadvantage of the more CO2 responsive forbs and N-fixing legumes.

An On-Chip Learning Method for Neuromorphic Systems Based on Non-Ideal Synapse Devices

In this paper, we propose an on-chip learning method that can overcome the poor characteristics of pre-developed practical synaptic devices, thereby increasing the accuracy of the neural network based on the neuromorphic system. The fabricated synaptic devices, based on Pr1−xCaxMnO3, LiCoO2, and TiOx, inherently suffer from undesirable characteristics, such as nonlinearity, discontinuities, and asymmetric conductance responses, which degrade the neuromorphic system performance. To address these limitations, we have proposed a conductance-based linear weighted quantization method, which controls conductance changes, and trained a neural network to predict the handwritten digits from the standard database MNIST. Furthermore, we quantitatively considered the non-ideal case, to ensure reliability by limiting the conductance level to that which synaptic devices can practically accept. Based on this proposed learning method, we significantly improved the neuromorphic system, without any hardware modifications to the synaptic devices or neuromorphic systems. Thus, the results emphatically show that, even for devices with poor synaptic characteristics, the neuromorphic system performance can be improved.

Room-Temperature Switching of Spin-State in Single-Molecule Junctions

The emerging of molecular spintronics offers a unique chance for the design of molecular devices with different spin-state, and the control of spin-state becomes essential for molecular spin switches. However, the intrinsic spin switching from low-spin to high-spin state is a temperature-dependent process with a small energy barrier that low temperature is required to maintain the low-spin state, and thus the room-temperature operation of single-molecule devices have not yet been achieved. Here, we investigated the single-molecule charge transport through a diamagnetic square planar nickel(II) porphyrin using the scanning tunneling microscope break-junction (STM-BJ) technique. The reversible single-molecule conductance switches are demonstrated by utilizing a coordination-induced spin-state switching to manipulate the spin state between S = 0 and S = 1 at room temperature. Furthermore, the different coordinated complexes could be distinguished from the conductance traces, which cannot be realized by the ensemble investigations such as NMR and UV-vis spectrums. The combined DFT calculations revealed that the conductance changes come from the different spin-states of the molecules varying the number of coordination ligands, suggesting coordination-induced spin-state switching provides a new way towards room-temperature molecular spintronics.