Effects of Ca 2+ on the Structure and Dynamics of PIP3 in Model Membranes Containing PC and PS.

Phosphatidylinositol phosphates (PIPs) are a family of seven different eukaryotic membrane lipids that have a large role in cell viability, despite their minor concentration in eukaryotic cellular membranes. PIPs tightly regulate cellular processes such as cellular growth, metabolism, immunity, and development through direct interactions with partner proteins. Understanding the biophysical properties of PIPs in the complex membrane environment is important to understand how PIPs selectively regulate a partner protein. Here we investigate the structure and dynamics of PIP3 in lipid bilayers that are simplified models of the natural membrane environment. We probe the effects of the anionic lipid phosphatidylserine (PS) and the divalent cation Ca 2+ . We use solution and solid-state 1 H, 31 P, and 13 C NMR all at natural abundance combined with MD simulations to characterize the structure and dynamics of PIPs. 1 H and 31 P 1D spectra show good resolution at high temperatures with isolated peaks in the headgroup, interfacial, and bilayer regions. Site specific assignment of these 1D reporters were made and used to measure the effects of Ca 2+ and PS. In particular, the resolved 31 P signals of the PIP3 headgroup allowed for extremely well localized information about PIP3 phosphate dynamics, which the MD simulations were able to help explain. Cross polarization kinetics provided additional site-specific dynamics measurements for the PIP3 headgroups.

Improved Detection of Target Metabolites in Brain Tumors with Intermediate TE, High SNR, and High Bandwidth Spin-Echo Sequence at 5T.

BACKGROUND AND PURPOSE: Due to high chemical shift displacement, challenges emerge at ultra-high fields when measuring metabolites using 1H-MRS. Our goal was to investigate how well the high SNR and high bandwidth spin-echo (HISE) technique perform at 5T for detecting target metabolites in brain tumors. MATERIALS AND METHODS: Twenty-six subjects suspected of having brain tumors were enrolled. HISE and point-resolved spectroscopy (PRESS) single-voxel spectroscopy scans were collected with a 5T clinical scanner with an intermediate TE (TE = 144 ms). The main metabolites, including total NAA, Cr, and total Cho, were accessed and compared between HISE and PRESS using a paired Student t test, with full width at half maximum and SNR as covariates. The detection rate of specific metabolites, including lactate, alanine, and lipid, and subjective spectral quality were accessed and compared between HISE and PRESS. RESULTS: Twenty-three pathologically confirmed brain tumors were included. Only the full width at half maximum for total NAA was significantly lower with HISE than with PRESS (P < .05). HISE showed a significantly higher SNR for total NAA, Cr, and total Cho compared with PRESS (P < .05). Lactate was detected in 21 of the 23 cases using HISE, but in only 4 cases using PRESS. HISE detected alanine in 8 of 9 meningiomas, whereas PRESS detected alanine in just 3 meningiomas. PRESS found lipid in more cases than HISE, while HISE outperformed PRESS in terms of subjective spectral quality. CONCLUSIONS: HISE outperformed the clinical standard PRESS technique in detecting target metabolites of brain tumors at 5T, particularly lactate and alanine.

Fluctuating magnetic droplets immersed in a sea of quantum spin liquid.

The search of quantum spin liquid (QSL), an exotic magnetic state with strongly fluctuating and highly entangled spins down to zero temperature, is a main theme in current condensed matter physics. However, there is no smoking gun evidence for deconfined spinons in any QSL candidate so far. The disorders and competing exchange interactions may prevent the formation of an ideal QSL state on frustrated spin lattices. Here we report comprehensive and systematic measurements of the magnetic susceptibility, ultralow-temperature specific heat, muon spin relaxation (µSR), nuclear magnetic resonance (NMR), and thermal conductivity for NaYbSe2 single crystals, in which Yb3+ ions with effective spin-1/2 form a perfect triangular lattice. All these complementary techniques find no evidence of long-range magnetic order down to their respective base temperatures. Instead, specific heat, µSR, and NMR measurements suggest the coexistence of quasi-static and dynamic spins in NaYbSe2. The scattering from these quasi-static spins may cause the absence of magnetic thermal conductivity. Thus, we propose a scenario of fluctuating ferrimagnetic droplets immersed in a sea of QSL. This may be quite common on the way pursuing an ideal QSL, and provides a brand new platform to study how a QSL state survives impurities and coexists with other magnetically ordered states.

In-situ construction of direct Z-scheme NiO/Bi2MoO6 heterostructure arrays with enhanced room temperature ether sensing properties under visible light irradiation.

Light irradiation has emerged as a promising strategy to promote room temperature sensing of resistive-type semiconductor gas sensors recently. However, high recombination rate of photo-generated carriers and poor visible light response of conventional semiconductor sensing materials have greatly limited the further performance improvement. It is urgent to develop gas sensing materials with high photo-generated carrier separation efficiency and excellent visible light response. Herein, a novel direct Z-scheme NiO/Bi2MoO6 heterostructure arrays were designed and in-situ constructed on alumina flat substrate to form thin film sensors, which realized excellent room temperature gas response towards ether under irradiation of visible light for the first time, together with excellent stability and selectivity. Based on density functional theory calculation and experimental characterization, it was demonstrated that the construction of Z-scheme heterostructure could greatly promote the separation of photo-generated carriers and adsorption of ether. Moreover, the excellent visible light response characteristics of NiO/Bi2MoO6 could improve the utilization of visible light. In addition, the in-situ construction of array structure could avoid a series of problems caused by the conventional thick film devices. The work not only provides a promising guideline for Z-scheme heterostructure arrays in promoting the room temperature sensing performance of semiconductors gas sensors under visible light irradiation, but also clarifies the gas sensing mechanism of Z-scheme heterostructure at the atomic and electronic level.

Peptide-Membrane Binding: Effects of the Amino Acid Sequence.

An understanding of how the amino acid sequence affects the interaction of peptides with lipid membranes remains mostly unknown. This type of knowledge is required to rationalize membrane-induced toxicity of amyloid peptides and to design peptides that can interact with lipid bilayers. Here, we perform a systematic study of how variations in the sequence of the amphipathic Ac-(FKFE)2-NH2 peptide affect its interaction with zwitterionic lipid bilayers using extensive all-atom molecular dynamics simulations in explicit solvent. Our results show that peptides with a net positive charge bind more frequently to the lipid bilayer than neutral or negatively charged sequences. Moreover, neutral amphipathic peptides made with the same numbers of phenylalanine (F), lysine (K), and glutamic (E) amino acids at different positions in the sequence differ significantly in their frequency of binding to the membrane. We find that peptides bind with a higher frequency to the membrane if their positive lysine side chains are more exposed to the solvent, which occurs if they are located at the extremity (as opposed to the middle) of the sequence. Non-polar residues play an important role in accounting for the adsorption of peptides onto the membrane. In particular, peptides made with less hydrophobic non-polar residues (e.g., valine and alanine) are significantly less adsorbed to the membrane compared to peptides made with phenylalanine. We also find that sequences where phenylalanine residues are located at the extremities of the peptide have a higher tendency to be adsorbed.

Atomic Insights into Amyloid-Induced Membrane Damage.

Amphipathic peptides can cause biological membranes to leak either by dissolving their lipid content via a detergent-like mechanism or by forming pores on the membrane surface. These modes of membrane damage have been related to the toxicity of amyloid peptides and to the activity of antimicrobial peptides. Here, we perform the first all-atom simulations in which membrane-bound amphipathic peptides self-assemble into ß-sheets that subsequently either form stable pores inside the bilayer or drag lipids out of the membrane surface. An analysis of these simulations shows that the acyl tail of lipids interact strongly with non-polar side chains of peptides deposited on the membrane. These strong interactions enable lipids to be dragged out of the bilayer by oligomeric structures accounting for detergent-like damage. They also disturb the orientation of lipid tails in the vicinity of peptides. These distortions are minimized around pore structures. We also show that membrane-bound ß-sheets become twisted with one of their extremities partially penetrating the lipid bilayer. This allows peptides on opposite leaflets to interact and form a long transmembrane ß-sheet, which initiates poration. In simulations, where peptides are deposited on a single leaflet, the twist in ß-sheets allows them to penetrate the membrane and form pores. In addition, our simulations show that fibril-like structures produce little damage to lipid membranes, as non-polar side chains in these structures are unavailable to interact with the acyl tail of lipids.

Synergistically Coupling of Manganese-Doped CoP Nanowires Arrays with Highly Dispersed Ni(PO3)2 Nanoclusters toward Efficient Overall Water Splitting.

Co-based phosphides are considered to be highly promising electrocatalysts for both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). However, their electrocatalytic efficiencies are greatly limited by the weak water dissociation process and unsatisfactory adsorption ability toward reaction intermediates. Herein, novel Mn-doped CoP/Ni(PO3)2 heterostructure array electrocatalysts which are composed of highly dispersed Ni(PO3)2 nanoclusters that are tightly wrapped on Mn-doped CoP nanowire arrays are designed. An electrocatalytic performance test suggested that the heterostructure arrays exhibited competitive electrocatalytic performance toward both HER and OER, which needed overpotentials of 116 and 245 mV to drive a current of 10 mA/cm2, respectively. Encouragingly, a symmetric two electrode water splitting system constructed by the heterostructure arrays required an ultralow cell voltage, suggesting the potential in overall water splitting. First-principles calculations combined with experimental characterization were further performed to clarify the electrocatalytic mechanism. On the one hand, effective doping of Mn atoms could optimize the surface electronic structure of CoP and promote the intrinsic activity. On the other hand, the compact and abundant heterogeneous interface between Ni(PO3)2 and CoP not only made more active sites exposed but also promoted the effective adsorption of intermediate reaction species on the catalyst surface. This work provides a new strategy to improve electrocatalytic performance of Co-based phosphides through the synergistic coupling of metal-doping and phosphate surface decoration, which will greatly promote the development of highly efficient electrocatalysts for overall water splitting.

Light-assisted room temperature gas sensing performance and mechanism of direct Z-scheme MoS2/SnO2 crystal faceted heterojunctions.

Light assistance and construction of heterojunctions are both promising means to improve the room temperature gas sensing performance of MoS2 recently. However, enhancing the separation efficiency of photo-generated carriers at interface and adsorption ability of surface have become the bottleneck problem to further improve the room temperature gas sensing performance of MoS2-based heterojunctions under light assistance. In the present study, a novel direct Z-scheme MoS2/SnO2 heterojunction was designed through crystal facets engineering and its room temperature gas sensing properties under light assistance was studied. It was found that the heterojunction showed outstanding room temperature NO2 sensing performance with a high response of 208.66 toward 10 ppm NO2, together with excellent recovery characteristics and selectivity. The gas sensing mechanism study suggested that high-energy {221} crystal facets of SnO2 and MoS2 directly formed Z-scheme heterojunction, which could greatly improve the separation efficiency of photo-generated carriers with high redox capacity. Moreover, {221} facets greatly enhanced adsorption ability towards NO2. This work not only opens up the application of Z-scheme heterojunctions in gas sensing, which will greatly promotes the development of room temperature light-assisted gas sensors, but also provides a new idea for the construction of direct Z-scheme heterojunctions through crystal facets engineering.

Highly Mesoporous Cobalt-Hybridized 2D Cu3P Nanosheet Arrays as Boosting Janus Electrocatalysts for Water Splitting.

Recently, developing economical electrocatalysts with high performance in water decomposition has become a research hotspot. Herein, two kinds of cobalt-hybridized Cu3P nanostructure array electrocatalysts (including highly mesoporous 2D nanosheets and sugar gourd-like 1D nanowires) were controllably grown on a nickel foam substrate through a simple hydrothermal method combined with a subsequent phosphating treatment method. An electrocatalytic test indicated that the as-prepared 2D nanosheet array exhibited excellent activity and stability toward hydrogen evolution reaction under alkaline conditions, which offered a low overpotential of 99 mV at 10 mA/cm2 and a small Tafel slope of 70.4 mV/dec, whereas a competitive overpotential of 272 mV was required for oxygen evolution reaction. In addition, the 2D nanosheet array delivered a low cell voltage of 1.66 V at 10 mA/cm2 in a symmetric two-electrode system, implying its huge potential in overall water decomposition. The electrocatalytic performance is superior to the as-prepared 1D nanowire array and most of the Cu3P-related electrocatalysts previously reported. Experimental measurements and first-principles calculations show that the excellent performance of the 2D nanosheet array can be attributed to its unique 2D mesoporous structure and hybridization of cobalt, which not only provide a large electrochemically active surface and fast electrocatalytic reaction kinetics but also weaken the binding strength of electrocatalytic reaction intermediates. The present study provides a simple and controllable approach to synthesize Cu3P-based bimetallic phosphide nanostructures, which can be used as boosting Janus electrocatalysts for water decomposition.

Binding Mechanisms of Amyloid-like Peptides to Lipid Bilayers and Effects of Divalent Cations.

In several neurodegenerative diseases, cell toxicity can emerge from damage produced by amyloid aggregates to lipid membranes. The details accounting for this damage are poorly understood including how individual amyloid peptides interact with phospholipid membranes before aggregation. Here, we use all-atom molecular dynamics simulations to investigate the molecular mechanisms accounting for amyloid-membrane interactions and the role played by calcium ions in this interaction. Model peptides known to self-assemble into amyloid fibrils and bilayer made from zwitterionic and anionic lipids are used in this study. We find that both electrostatic and hydrophobic interactions contribute to peptide-bilayer binding. In particular, the attraction of peptides to lipid bilayers is dominated by electrostatic interactions between positive residues and negative phosphate moieties of lipid head groups. This attraction is stronger for anionic bilayers than for zwitterionic ones. Hydrophobicity drives the burial of nonpolar residues into the interior of the bilayer producing strong binding in our simulations. Moreover, we observe that the attraction of peptides to the bilayer is significantly reduced in the presence of calcium ions. This is due to the binding of calcium ions to negative phosphate moieties of lipid head groups, which leaves phospholipid bilayers with a net positive charge. Strong binding of the peptide to the membrane occurs less frequently in the presence of calcium ions and involves the formation of a "Ca2+ bridge".

Role of Cholesterol on Binding of Amyloid Fibrils to Lipid Bilayers.

Molecular dynamics simulations are used to provide insights into the molecular mechanisms accounting for binding of amyloid fibrils to lipid bilayers and to study the effect of cholesterol in this process. We show that electrostatic interactions play an important role in fibril-bilayer binding and cholesterol modulates this interaction. In particular, the interaction between positive residues and lipid head groups becomes more favorable in the presence of cholesterol. Consistent with experiments, we find that cholesterol enhances fibril-membrane binding.