Dynamic Interface Research Articles

The Self-Association of the KRAS4b Protein is Altered by Lipid-Bilayer Composition and Electrostatics.

KRAS is a peripheral membrane protein that regulates multiple signaling pathways, and is mutated in ≈30 % of cancers. Transient self-association of KRAS is essential for activation of the downstream effector RAF and oncogenicity. The presence of anionic phosphatidylserine (PS) lipids in the membrane was shown to promote KRAS self-assembly, however, the structural mechanisms remain elusive. Here, we employed nanodisc bilayers of defined lipid compositions, and probed the impact of PS concentration on KRAS self-association. Paramagnetic NMR experiments demonstrated the existence of two transient dimer conformations involving alternate electrostatic contacts between R135 and either D153 or E168 on the "α4/5-α4/5" interface, and revealed that lipid composition and salt modulate their dynamic equilibrium. These dimer interfaces were validated by charge-reversal mutants. This plasticity demonstrates how the dynamic KRAS dimerization interface responds to the environment, and likely extends to the assembly of other signaling complexes on the membrane.

The Self‐Association of the KRAS4b Protein is Altered by Lipid‐Bilayer Composition and Electrostatics

AbstractKRAS is a peripheral membrane protein that regulates multiple signaling pathways, and is mutated in ≈30 % of cancers. Transient self‐association of KRAS is essential for activation of the downstream effector RAF and oncogenicity. The presence of anionic phosphatidylserine (PS) lipids in the membrane was shown to promote KRAS self‐assembly, however, the structural mechanisms remain elusive. Here, we employed nanodisc bilayers of defined lipid compositions, and probed the impact of PS concentration on KRAS self‐association. Paramagnetic NMR experiments demonstrated the existence of two transient dimer conformations involving alternate electrostatic contacts between R135 and either D153 or E168 on the “α4/5‐α4/5” interface, and revealed that lipid composition and salt modulate their dynamic equilibrium. These dimer interfaces were validated by charge‐reversal mutants. This plasticity demonstrates how the dynamic KRAS dimerization interface responds to the environment, and likely extends to the assembly of other signaling complexes on the membrane.

Phase-Changeable Dynamic Conformal Electrode/electrolyte Interlayer enabling Pressure-Independent Solid-State Lithium Metal Batteries.

Lithium-metal-based solid-state batteries (Li-SSBs) are one of the most promising energy storage devices due to their high energy densities. However, under insufficient pressure constraints (<MPa-level), Li-SSBs usually exhibit poor electrochemical performances owing to the continuous interfacial degradation between the solid-state electrolyte (SSE) and electrodes. Herein, a phase-changeable interlayer is developed to construct the self-adhesive and dynamic conformal electrode/SSE contact in Li-SSBs. The strong adhesive and cohesive strengths of the phase-changeable interlayer enable Li-SSBs to resist up to 250 N pulling force (=1.9MPa), affording Li-SSBs ideal interfacial integrality even without extra stack pressure. Remarkably, this interlayer exhibits a high ionic conductivity of 1.3 ×10-3 S cm-1 , attributed to the shortened steric solvation hindrance and optimized Li+ coordination structure. Furthermore, the changeable phase property of the interlayer endows Li-SSBs with a healable Li/SSE interface, accommodating the stress-strain evolution of the lithium metal and constructing the dynamic conformal interface. Consequently, the contact impedance of the modified solid symmetric cell exhibits a pressure-independent manner and does not increase over 700h (0.2MPa). The LiFePO4 pouch cell with the phase-changeable interlayer shows 85% capacity retention after 400 cycles at a low pressure of 0.1MPa.

Unlocking the Polarization and Reversibility Limitations for Stable Low‐Temperature Lithium Metal Anodes

The subzero‐temperature service of lithium (Li) metal anode has been enormously restricted by a large working polarization and a poor reversibility. In this contribution, the overpotential attributions during low‐temperature Li electroplating are deconvolved, and the interplay among the dominating kinetic overpotential, the dynamic solid electrolyte interphase (SEI) chemistry, and the corresponding cycling reversibility of Li metal is established. Specifically, by employing a localized highly concentrated electrolyte as a model system, it is disclosed that ionic concentration gradient plays a predominate role in polarizing the cathodic Li electroplating process at subzero working temperature. Inspired by this, a decoupling electrolyte design strategy is presented to synchronously tame the kinetic polarization and build a dynamically stable anion‐derived SEI, thus boosting a remarkably enhanced Coulombic efficiency of Li with a depressed cell overpotential and a more than three times longer lifespan in practical Li | LiNi0.5Co0.2Mn0.3O2 cells at −20 °C. Herein, the essence to affecting the polarization and reversibility of low‐temperature working Li metal anode is uncovered, affording critical design principles to facilitate a stable dynamic interface for the high‐efficiency cycling of practical Li metal batteries at subzero temperatures.

PH‐Triggered Molecular Switch Toward Texture‐Regulated Zn Anode

AbstractZn electrodes in aqueous media exhibit an unstable Zn/electrolyte interface due to severe parasitic reactions and dendrite formation. Here, a dynamic Zn interface modulation based on the molecular switch strategy is reported by hiring γ‐butyrolactone (GBL) in ZnCl2/H2O electrolyte. During Zn plating, the increased interfacial alkalinity triggers molecular switch from GBL to γ‐hydroxybutyrate (GHB). GHB strongly anchors on Zn surface via triple Zn−O bonding, leading to suppressive hydrogen evolution and texture‐regulated Zn morphology. Upon Zn stripping, the fluctuant pH turns the molecular switch reaction off through the cyclization of GHB to GBL. This dynamic molecular switch strategy enables high Zn reversibility with Coulombic efficiency of 99.8 % and Zn||iodine batteries with high‐cyclability under high Zn depth of discharge (50 %). This study demonstrates the importance of dynamic modulation for Zn electrode and realizes the reversible molecular switch strategy to enhance its reversibility.

PH-Triggered Molecular Switch Toward Texture-Regulated Zn Anode.

Zn electrodes in aqueous media exhibit an unstable Zn/electrolyte interface due to severe parasitic reactions and dendrite formation. Here, a dynamic Zn interface modulation based on the molecular switch strategy is reported by hiring γ-butyrolactone (GBL) in ZnCl2 /H2 O electrolyte. During Zn plating, the increased interfacial alkalinity triggers molecular switch from GBL to γ-hydroxybutyrate (GHB). GHB strongly anchors on Zn surface via triple Zn-O bonding, leading to suppressive hydrogen evolution and texture-regulated Zn morphology. Upon Zn stripping, the fluctuant pH turns the molecular switch reaction off through the cyclization of GHB to GBL. This dynamic molecular switch strategy enables high Zn reversibility with Coulombic efficiency of 99.8 % and Zn||iodine batteries with high-cyclability under high Zn depth of discharge (50 %). This study demonstrates the importance of dynamic modulation for Zn electrode and realizes the reversible molecular switch strategy to enhance its reversibility.

Generalized total internal reflection at dynamic interfaces

Recent research developments in the area of spacetime metamaterial structures and systems have raised new questions as to how the physics of fundamental phenomena is altered in the presence of spacetime modulation. In this context, we present a generalized and comparative description of the phenomenon of total internal reflection (TIR) at different dynamic interfaces. Such interfaces include, beyond the classical interfaces corresponding to the boundaries of moving bodies (moving interface--moving matter systems), interfaces formed by a traveling-wave step modulation of an electromagnetic parameter (e.g., refractive index) (moving interface--stationary matter systems) and fixed interfaces between moving-matter media (stationary interface--moving matter systems). We first resolve the problem using the evanescence of the transmitted wave as the criterion for TIR and applying the conventional technique of relative frame hopping (between the laboratory and rest frames), which results in closed-form formulas for the relevant critical (incidence, reflection, phase refraction, and power refraction) angles. We then introduce the concept of catch-up limit between the dynamic interface and the transmitted wave as an alternative criterion for the critical angle. We use this approach both to analytically verify the critical angle formulas, further validated by full-wave (FDTD) analysis, and to explain the related physics, using Fresnel-Fizeau drag and spacetime frequency transition considerations. These results might find various applications in ultrafast optics, gravity analogs, and quantum processing.

Entrepreneurial Behaviour and Organisational Propensity to Innovate in a Public-Sector Context

The importance of innovation, in both private and public entrepreneurial fields, is the basis of all companies’ strategic choices. This study examines entrepreneurship and innovation, as well as their dynamic interface in value creation, in the public sector. It explores entrepreneurial determinants for public-sector innovation, as collected from managers and employees involved in the water supply and sewage industries in Ukraine. The data, related to a sample of firms, were obtained from a twofold self-administered survey. Adopting an ordered logistic regression model to analyse the data obtained from a survey, it is found that the entrepreneurial determinants of self-awareness, knowledge-enabling and entrepreneurial orientation positively correlate with fostering innovation process. The findings reveal that entrepreneurial leadership and intrapreneurial self-efficacy are mediating determinants. Finally, the results demonstrate that intrapreneurial self-efficacy has more potential than entrepreneurial leadership to stimulate innovation at the individual level, which has both theoretical and practical implications.

Blood-Brain Barrier Dysfunction in Normal Aging and Neurodegeneration: Mechanisms, Impact, and Treatments.

Cerebral endothelial cells and their linking tight junctions form a unique, dynamic and multi-functional interface, the blood-brain barrier (BBB). The endothelium is regulated by perivascular cells and components forming the neurovascular unit. This review examines BBB and neurovascular unit changes in normal aging and in neurodegenerative disorders, particularly focusing on Alzheimer disease, cerebral amyloid angiopathy and vascular dementia. Increasing evidence indicates BBB dysfunction contributes to neurodegeneration. Mechanisms underlying BBB dysfunction are outlined (endothelium and neurovascular unit mediated) as is the BBB as a therapeutic target including increasing the uptake of systemically delivered therapeutics across the BBB, enhancing clearance of potential neurotoxic compounds via the BBB, and preventing BBB dysfunction. Finally, a need for novel biomarkers of BBB dysfunction is addressed.

A New Identifying Strategy for 6-DOF Dynamic Interface Force Based on Strain Monitoring

A New Identifying Strategy for 6-DOF Dynamic Interface Force Based on Strain Monitoring

Interfacial microstructure evolution and mechanical properties of AlCoCrFeNi2.1 alloy by multilayer additive hot compression bonding

Multilayer additive hot-compression bonding (MAHCB) is an efficient manufacturing method for obtaining a large alloy with a uniform composition and microstructure. In this work, the method was applied to an AlCoCrFeNi2.1 eutectic alloy for the first time. The results show that the bonding temperature significantly affects the interface microstructure, improving dynamic recrystallization (DRX) and interface grain boundary migration (GBM), as well as reducing defects at the interface. Optimal bonding was obtained at a bonding temperature of 1250 °C. The interfacial Vickers hardness reaches 317 HV, and the tensile‒shear strength reaches 894 MPa, which are 9.3% and 16.5% improved, respectively, compared with the as-cast sample. The interface microstructure and fracture morphology are very close to those of the as-cast state. The combination of temperature and strain promote the interfacial bonding process, which mainly include DRX in the FCC phases, element diffusion between the FCC and B2 phases, and transformation of harmful B2–B2 interfaces into those of FCC-B2 type.

A verified analytical sandwich beam model for soft and hard cores: comparison to existing analytical models and finite element calculations

This paper presents a novel approach of modeling of three-layer beam. Such composites are usually known as sandwich structures if the modulus of elasticity of the core is much smaller than those of the faces. In the present approach, the faces are modeled as Bernoulli–Euler beams, the core as a Timoshenko beam. Taking into account the kinematic and dynamic interface conditions, which means that the perfect bonding assumptions hold for the displacement and each layer is subjected to continuous traction stresses across the interface, a sixth-order differential equation is derived for the bending deflection, and a second-order system for the axial displacement. No restrictions are imposed on the elastic properties of the middle layer, and hence the developed theory also yields accurate results for hard cores. The presented refined theory is compared to analytical models from the literature and to finite element calculations for various benchmark examples. Special focus is laid the boundary conditions and the core stiffness. A parametric study varying the Young modulus of the core shows that the present sandwich model agrees very well with the target solutions obtained from finite element calculations under plane stress assumptions, in particular concerning the transverse deflection, the shear stress distribution and the interfacial normal stress.

Near-Infrared Spectroscopy for the In Vivo Monitoring of Biodegradable Implants in Rats.

Magnesium (Mg) alloys possess unique properties that make them ideal for use as biodegradable implants in clinical applications. However, reports on the in vivo assessment of these alloys are insufficient. Thus, monitoring the degradation of Mg and its alloys in vivo is challenging due to the dynamic process of implant degradation and tissue regeneration. Most current works focus on structural remodeling, but functional assessment is crucial in providing information about physiological changes in tissues, which can be used as an early indicator of healing. Here, we report continuous wave near-infrared spectroscopy (CW NIRS), a non-invasive technique that is potentially helpful in assessing the implant-tissue dynamic interface in a rodent model. The purpose of this study was to investigate the effects on hemoglobin changes and tissue oxygen saturation (StO2) after the implantation of Mg-alloy (WE43) and titanium (Ti) implants in rats' femurs using a multiwavelength optical probe. Additionally, the effect of changes in the skin on these parameters was evaluated. Lastly, combining NIRS with photoacoustic (PA) imaging provides a more reliable assessment of tissue parameters, which is further correlated with principal component analysis.

Reconsidering the role of blood-brain barrier in Alzheimer's disease: From delivery to target.

The existence of a selective blood-brain barrier (BBB) and neurovascular coupling are two unique central nervous system vasculature features that result in an intimate relationship between neurons, glia, and blood vessels. This leads to a significant pathophysiological overlap between neurodegenerative and cerebrovascular diseases. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease whose pathogenesis is still to be unveiled but has mostly been explored under the light of the amyloid-cascade hypothesis. Either as a trigger, bystander, or consequence of neurodegeneration, vascular dysfunction is an early component of the pathological conundrum of AD. The anatomical and functional substrate of this neurovascular degeneration is the BBB, a dynamic and semi-permeable interface between blood and the central nervous system that has consistently been shown to be defective. Several molecular and genetic changes have been demonstrated to mediate vascular dysfunction and BBB disruption in AD. The isoform ε4 of Apolipoprotein E is at the same time the strongest genetic risk factor for AD and a known promoter of BBB dysfunction. Low-density lipoprotein receptor-related protein 1 (LRP-1), P-glycoprotein, and receptor for advanced glycation end products (RAGE) are examples of BBB transporters implicated in its pathogenesis due to their role in the trafficking of amyloid-β. This disease is currently devoid of strategies that change the natural course of this burdening illness. This unsuccess may partly be explained by our misunderstanding of the disease pathogenesis and our inability to develop drugs that are effectively delivered to the brain. BBB may represent a therapeutic opportunity as a target itself or as a therapeutic vehicle. In this review, we aim to explore the role of BBB in the pathogenesis of AD including the genetic background and detail how it can be targeted in future therapeutic research.

Super-Resolution Imaging of Bacterial Secreted Proteins Using Genetic Code Expansion.

Type three secretion systems (T3SSs) enable gram-negative bacteria to inject a battery of effector proteins directly into the cytosol of eukaryotic host cells. Upon entry, the injected effector proteins cooperatively modulate eukaryotic signaling pathways and reprogram cellular functions, enabling bacterial entry and survival. Monitoring and localizing these secreted effector proteins in the context of infections provides a footprint for defining the dynamic interface of host-pathogen interactions. However, labeling and imaging bacterial proteins in host cells without disrupting their structure/function is technically challenging. Constructing fluorescent fusion proteins does not resolve this problem, because the fusion proteins jam the secretory apparatus and thus are not secreted. To overcome these obstacles, we recently employed a method for site-specific fluorescent labeling of bacterial secreted effectors, as well as other difficult-to-label proteins, using genetic code expansion (GCE). This paper provides a complete step-by-step protocol to label Salmonella secreted effectors using GCE site-specifically, followed by directions for imaging the subcellular localization of secreted proteins in HeLa cells using direct stochastic optical reconstruction microscopy (dSTORM) Recent findings suggest that the incorporation of non-canonical amino acids (ncAAs) via GCE, followed by bio-orthogonal labeling with tetrazine-containing dyes, is a viable technique for selective labeling and visualization of bacterial secreted proteins and subsequent image analysis in the host. The goal of this article is to provide a straightforward and clear protocol that can be employed by investigators interested in conducting super-resolution imaging using GCE to study various biological processes in bacteria and viruses, as well as host-pathogen interactions.

Flow Evolution and Energy Loss Mechanism in Accidental Shutdown Process of a Large Submersible Mixed-Flow Pump System

To investigate the accidental shutdown process for a large vertical and submersible mixed-flow pump unit in a drainage pumping station, a three-dimensional numerical method for this transition process was proposed according to the angular momentum balance theorem and rigid body rotation technology. We obtained the transient performance curves of the unit and the internal flow characteristics of the full flow channel. In addition, we also analyzed the energy loss distribution of the through-flow components during this progress based on the entropy production theory. The results show that the whole runaway process needs to go through four stages: the pump mode, the pump braking mode, the turbine mode, and the stable runaway mode. The pressure amplitude changes greatly in impeller and guide vanes, and the main fluctuation frequency is the blade frequency. There are higher harmonic frequencies in the dynamic rotor-stator interface. As the rotating speed increases in turbine mode, the negative pressure area near the impeller blade’s trailing edge gradually increases. The entropy production method can be used to determine the location, intensity of energy loss during the transient process. If the rotating speed exceeds the allowed value in the runaway turbine mode, the interaction between blade tip vortex and hub vortex rope may cause loss of stability.

Molecular models of heme transfer in C. diphtheriae.

Corynebacterium diphtheriae is a bacteria that uses iron to assist in its survival and proliferation. It commonly obtains iron from host hemoglobin or the hemoglobin-haptoglobin complex. The protein pathway of the heme transport contains multiple proteins, including HbpA, ChtA, HtaA, HtaB, and HmuT, and the heme is shuttled between these proteins through a process that likely involves the formation of multiple transient protein/protein interfaces. However, the molecular mechanisms underlying heme acquisition and transport in these multimeric complexes remains unknown. To better understand these iron acquisition dynamics, we have performed a series of molecular dynamic (MD) simulations along the C. diphtheriae heme transfer pathway starting from unique rigid body docking structures, and used them to produce Markov State Models that reveal the kinetics and thermodynamics of the protein/protein association complexes. Results show a dynamic protein interface reveals intricacies of the heme acquisition process on the microsecond timescale.

Multimodal interactions between a disordered protein and its folded target at single-molecule level.

Cap-dependent initiation of translation is regulated by the interaction of the eukaryotic translation initiation factor 4E (eIF4E) with the 120-residue disordered eIF4E binding protein 2 (4E-BP2) in a phosphorylation-dependent manner. In a previous NMR study (Lukhele et al., Structure 2013) we showed that 4E-BP2 interacts with eIF4E via a dynamic bipartite interface consisting of a α-helical primary binding site and a disordered secondary binding site.In our recent paper (Smyth et al., Biophys. J., 2022) we used single-molecule fluorescence resonance energy transfer (smFRET) to show that the conformational changes of 4E-BP2 induced by binding to eIF4E are non-uniform along the sequence; a central region containing both motifs that bind to eIF4E expands and becomes stiffer, the C-terminal region is less affected. In the same paper, segmental chain dynamics and non-local intrachain contacts were measured via fluorescence anisotropy decay and fluorescence correlation spectroscopy, respectively. Surprisingly, we found that the chain dynamics around sites in the C-terminal region, far away from the two known binding motifs, were significantly reduced upon binding to eIF4E, suggesting that this region is also involved in the highly dynamic 4E-BP2:eIF4E complex. Intermolecular smFRET was used to study the interaction between donor-labelled, surface-immobilized eIF4E and acceptor-labelled, freely diffusing 4E-BP2. FRET efficiency-time trajectories from thousands of individual molecules were used to derive the distributions of on- and off-binding times (τON and τOFF) at the sub-ensemble level. We hypothesize that the C-terminal region of 4E-BP2 engages in transient interactions with the disordered N-terminal region of eIF4E. Intermolecular smFRET was measured for different pairs of labelling sites on eIF4E and 4E-BP2. These data provide important new clues about the architecture and the dynamics 4E-BP2:eIF4E complex and can be used as highly informative restraints in computational ensemble modelling approaches.

I shall be released: Assembly platform dynamics during type II secretion

In this issue of Structure, Dazzoni etal. solve the high-resolution homo- and hetero-dimeric structures of the Klebsiella oxytoca PulL and PulM C-terminal domains and unravel an uncharacterized dynamic interaction interface that is required for correct function of the type II secretion system.

2D Dynamic Heterogeneous Interface Coupling Endowing Extra Zn2+ Storage

AbstractAqueous zinc‐ion battery (AZIBs) is expected to be an ideal device for large‐scale energy storage for its high safety and low cost. However, it is still a challenge to achieve both high energy density and high stability. Herein, in situ liquid‐phase growth exfoliation is developed to obtain V5O12 nanosheets, which is then combined with Ti3C2 nanosheets to construct two‐dimensional heterostructure (2D HVO@Ti3C2) with interfacial VOTi bonds. 2D HVO@Ti3C2 exhibits a dynamic interface coupling during discharging/charging, accompanied by break/reconstruction of interfacial VOTi bonds. The dynamic interface coupling provides a reversible electron transfer channel and endows the inert Ti3C2 with electrochemical activity in AZIBs, making it an additional electron acceptor and donor, and promoting the insertion of more Zn2+. Therefore, a capacity beyond the theoretical capacity of HVO is obtained for the HVO@Ti3C2. Additionally, the reversible 2D dynamic interface coupling can also effectively alleviate the structural damage during the cycling process. Then, the ultra‐high capacity (457.1 mAh g‐1 at 0.2 A g‐1, over 600 mAh g‐1 based on the mass of HVO) and high stability (88.9% capacity retention after 1000 cycles at 5 A g‐1) are achieved. This interface coupling mechanism provides an exciting strategy for the high energy density and high stability of AZIBs.