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Purpose Previous studies have shown that the presence of EGFR T790M mutation may reduce the treatment efficacy of tyrosine kinase inhibitors (TKIs) in EGFR-mutant lung cancer. However, little is known about the clinical features and outcomes of EGFR T790M mutation in pretreated patients with NSCLC. Patients and methods The clinical features of EGFR-activating and T790M mutations were assessed in a large cohort of patients with EGFR-TKI-naive NSCLC (all/EGFR mutations, n=16,347/7,687). The correlation between the pretreatment T790M mutation status and clinical outcomes was evaluated using univariate and multivariate analyses. Results Pretreatment T790M mutation was reported in 1.39% of the patients and coexisted with an EGFR-activating or uncommon mutation. The dual EGFR T790M and common EGFR-activating mutations were more likely to be detected in lung adenocarcinoma, whereas single T790M mutation was more prevalent in non-adenocarcinomas. The presence of de novo T790M mutation correlated with reduced recurrence-free survival (RFS) in patients with NSCLC (odds ratio [OR] 3.37, 95% confidence interval [CI] 1.67-6.79, P = 0.001). After molecular stratification, T790M mutation was shown to exert adverse effects on the RFS of EGFR 19-del group (OR 2.89, 95% CI 1.10-7.91, P = 0.028) and EGFR L858R group (OR 3.43, 95% CI 1.33-8.88, P = 0.013). Furthermore, pretreatment T790M mutation promoted tumor metastasis to different sites. Conclusion T790M-positive tumors presented special clinical features, and the coexistence of T790M and common EGFR-activating mutations was associated with poor prognosis in patients with NSCLC.

Doping in organic–inorganic perovskite semiconductors is an effective method to tailor their optoelectronic properties. In this work, manganese-doped perovskite films with different Mn/Pb ratios ranging from 0% to 2% were systematically studied. The device performance of 0.2% Mn-doped devices was improved compared to that of a device without Mn. However, a further increase of the doping concentration induced a decrease in performance. Several characteristics (especially different scanning probe microscopy characteristics) reveal that an increased dopant concentration results in reduced crystallinity and a change in the film morphology and causes a deterioration in photovoltaic performance for higher dopant concentrations. In the best-performing samples (0.2%), a shift in the valence band level and band gap are found which are responsible for the increased open circuit voltage, while increased grain boundaries and lower surface charge density are responsible for a small reduction in the short circuit current. Thus, multifunctional scanning probe microscopy approaches, combined with different film characterization techniques, offer us effective tools to investigate the impact of doping in the perovskite materials and the corresponding device performance.

Anisotropic Sb2Se3 is an emerging earth-abundant photocathode for photoelectrochemical water splitting. However, controlling the growth of the Sb2Se3 film with optimal [001] crystallographic orientation is still the most challenging issue. Here, we successfully synthesized [001]-oriented Sb2Se3via a reliable and facile method. The [001]-oriented Sb2Se3 film could provide an excellent carrier-migration efficiency. Consequently, we achieved a record-high photocurrent density of -20.2 mA cm-2 at 0 VRHE and a very high half-cell solar-to-hydrogen efficiency of 1.36% under 1-sun simulated solar illumination in a TiO2/[001]-Sb2Se3 photocathode. This work provides an effective strategy and important guidelines for rationally designing optoelectronic devices based on the [001]-oriented Sb2Se3 film.

Anisotropic Sb

Cell migration through anisotropic microenvironment is critical to a wide variety of physiological and pathological processes. However, adequate analytical tools to derive motile parameters to characterize the anisotropic migration are lacking. Here, we proposed a method to obtain the four motile parameters of migration cells based on the anisotropic persistent random walk model which is described by two persistence times and two migration speeds at perpendicular directions. The key process is to calculate the velocity power spectra of cell migration along intrinsically perpendicular directions respectively, then to apply maximum likelihood estimation to derive the motile parameters from the power spectra fitting with double exponential decay. The simulation results show that the averaged persistence times and the corrected migration speeds can be good estimations for motile parameters of cell migration.

Various kinds of semiconductor materials, organic and inorganic, served effectively as electrons or holes transport materials for perovskite solar cells (PSCs). However, their direct function has rarely been reported other than examining their effect in the final photovoltaic devices. In this work, a general and facile method was employed to determine to a point the type of carriers transferred by both SnO2 and NiO popular charge transport materials in PSCs via scanning Kelvin probes microscopy. The sign of the increment of the surface potential voltage measured tells directly whether electrons or holes were extracted by these carrier transport materials while its mapping can also provide the extraction difference between grain interiors and grain boundaries. Both MAPbI3 and CsFAMA triple cation perovskites were involved in the test with the same conclusion. Along with time-resolved photoluminescence, the extraction rate of each kind of material can be distinguished. This work definitely offers us a gener...

Understanding the mechanisms underlying the diversity of tumor invasion dynamics, including single-cell migration, multicellular streaming, and the emergence of various collective migration patterns, is a long-standing problem in cancer research. Here we have designed and fabricated a series of microchips containing high-throughput microscale tracks using protein repelling coating technology, which were then covered with a thin Matrigel layer. By varying the geometrical confinement (track width) and microenvironment factors (Matrigel concentration), we have reproduced a diversity of collective migration patterns in the chips, which were also observed in vivo. We have further classified the collective patterns and quantified the emergence probability of each class of patterns as a function of microtrack width and Matrigel concentration to devise a quantitive "collective pattern diagram." To elucidate the mechanisms behind the emergence of various collective patterns, we employed cellular automaton simulations, incorporating the effects of both direct cell-cell interactions and microenvironment factors (e.g., chemical gradient and extracellular matrix degradation). Our simulations suggest that tumor cell phenotype heterogeneity, and the associated dynamic selection of a favorable phenotype via cell-microenivronment interactions, are key to the emergence of the observed collective patterns in vitro.

Cell migration in fibrous extracellular matrix (ECM) is crucial to many physiological and pathological processes such as tissue regeneration, immune response, and cancer progression. During migration, individual cells can generate active pulling forces via actomyosin contraction, which are transmitted to the ECM fibers through focal adhesion complexes, remodel the ECM, and eventually propagate to and can be sensed by other cells in the system. The microstructure and physical properties of the ECM can also significantly influence cell migration, e.g., via durotaxis and contact guidance. Here, we develop a computational model for two-dimensional cell migration regulated by cell-ECM micromechanical coupling. Our model explicitly takes into account a variety of cellular-level processes, including focal adhesion formation and disassembly, active traction force generation and cell locomotion due to actin filament contraction, transmission and propagation of tensile forces in the ECM, as well as the resulting ECM remodeling. We validate our model by accurately reproducing single-cell dynamics of MCF-10A breast cancer cells migrating on collagen gels and show that the durotaxis and contact guidance effects naturally arise as a consequence of the cell-ECM micromechanical interactions considered in the model. Moreover, our model predicts strongly correlated multicellular migration dynamics, which are resulted from the ECM-mediated mechanical coupling among the migrating cell and are subsequently verified in in vitro experiments using MCF-10A cells. Our computational model provides a robust tool to investigate emergent collective dynamics of multicellular systems in complex in vivo microenvironment and can be utilized to design in vitro microenvironments to guide collective behaviors and self-organization of cells.

Cell migration is essential for regulating many biological processes in physiological or pathological conditions, including embryonic development and cancer invasion. In vitro and in silico studies suggest that collective cell migration is associated with some biomechanical particularities such as restructuring of extracellular matrix (ECM), stress and force distribution profiles, and reorganization of the cytoskeleton. Therefore, the phenomenon could be understood by an in-depth study of cells' behavior determinants, including but not limited to mechanical cues from the environment and from fellow "travelers". This review article aims to cover the recent development of experimental and computational methods for studying the biomechanics of collective cell migration during cancer progression and invasion. We also summarized the tested hypotheses regarding the mechanism underlying collective cell migration enabled by these methods. Together, the paper enables a broad overview on the methods and tools currently available to unravel the biophysical mechanisms pertinent to cell collective migration as well as providing perspectives on future development toward eventually deciphering the key mechanisms behind the most lethal feature of cancer.

Single molecule techniques emerge as powerful and quantitative approaches for scientific investigations in last decades. Among them, single molecule fluorescence spectroscopy (SMFS) is able to non-invasively characterize and track samples at the molecular level. Here, applications of SMFS to fundamental biological questions have been briefly summarized in catalogues of single-molecule counting, distance measurements, force sensors, molecular tracking, and ultrafast dynamics. In these SMFS applications, statistics and physical laws are utilized to quantitatively analyze the behaviors of biomolecules in cellular signaling pathways and the mechanisms of biological functions. This not only deepens our understanding of bio-systems, but also provides a fresh angle to those fundamental questions, leading to a more quantitative thinking in life science.

Based on the combined technologies of atomic force microscopy, X-ray diffraction/scattering, Fourier transform infrared spectra analysis, etc., it is demonstrated that the nano-fishnet-like networks, one of the most flexible but toughest structures, turn out to be the basic structure of silk filaments. The force patterns of pulling individual fibrils allow the identification of the pathways of unfolding protein segments in stacking β-crystallites, which reveal the fishnet-like topology. The calculation shows that the β-crystallites in silk nanofibrils are the cross-linking points of the nano-fishnets, which may enhance the toughness of silk filaments up to 1000 times, compared with amyloid-like and unlinked string structures. It follows that the strong β-sheet–β-sheet interaction, a high degree of ordering, and a high density of β-crystallites in silk fibers toughen the fishnet structure, then strengthen silk filaments, in consistency with the experiments for both spider and silkworm silks. The knowledge on the fishnet structure of silk fibers sheds light on the design and synthesis of either protein or synthetic fibers of ultraperformance in a more generic way.

Mechanosensing of the micro-environments has been shown to be essential for cell survival, growth, differentiation and migration. The mechanosensing pathways are mediated by a set of mechanosensitive proteins located at focal adhesion and cell-cell adherens junctions as well as in the cytoskeleton network. Here we review the applications of magnetic tweezers on elucidating the molecular mechanisms of the mechanosensing proteins. The scope of this review includes the principles of the magnetic tweezers technology, theoretical analysis of force-dependent stability and interaction of mechanosensing proteins, and recent findings obtained using magnetic tweezers.

The impact of the nanostructures of conjugated polymers on their electronic properties is significant. We notice that poly(3-hexylthiophene-2,5-diyl) (P3HT) can form nano-islands and nano-fibrils, and both of them show an similar single-layer thickness (∼1.5–1.6 nm) as evaluated by atomic force microscopy (AFM). The Raman spectra indicate the highest degree of chain planarity and crystallinity in the nano-islands. By using scanning Kelvin probe microscopy (SKPM) and electrostatic force microscopy (EFM), we image the surface potential at the nanometer scale and quantitatively estimate the charges on these nanostructures as modulated by light. Both results are consistent with each other: the surface potential increases on switching on the light, and the photo-induced charges are around 15–25% and positive. A similar amount of the photo-induced charges in both P3HT islands and fibril is consistent with the π–π stacking nature of these nanostructures. As P3HT is a hole-conducting molecule, positive charges are found easily injected into a single island by a positively biased EFM tip, and then the injected charges are able to propagate all over the island.

Based on mixed piezoelectric and ferroelectric nanostructures with polymers in various architectural forms, the flexible triboelectric nanogenerators (TENGs) have been extensively investigated. In this study, we design and fabricate lead-free ZnSnO 3 nanocubes @ polydimethylsiloxane (PDMS) based TENG by dispersing ZnSnO 3 nanocubes into PDMS elastomer at different ratios. Finally, the TENG can attain a maximum electrical output signal up to 400 V and 28 μA at a current density of 7 μA cm −2 , and an effective power to 3 mW at 6 wt% mass ZnSnO 3 mixed into PDMS. The harvested energy is utilized to drive 106 blue LEDs. In addition, this TENG generates stable electric power, even in the compressing-and-releasing process for over 500 cycles. Further investigation by electrostatic force microscopy shows clearly the maximum surface charge density appears at the optimal mixing ratio of ZnSnO 3 piezoelectric nanostructures into PDMS. This demonstrates that the optimization of the mixing ration between ZnSnO 3 piezoelectric nanostructures and PDMS is an effective method to increase the surface charges on the composite thin film and then improve the performance of the TENG. This TENG technology reveals a great candidate to be applied in large-scale device fabrications, flexible sensors and biological devices because of its easy fabrication process, high output power and biocompatibility.

Background Metastasis determines the lethality of cancer. In most clinical cases, patients are able to live with tumor proliferation before metastasis. Thus, the transition from tumor proliferation to metastasis/invasion is essential. However, the mechanism is still unclear and especially, the proliferation-to-metastasis/invasion transition point has not been well defined. Therefore, quantitative characterization of this transition is urgently needed. Methods We have successfully developed a home-built living-cell incubation system combined with an inverted optical microscope, and a systematic, quantitative approach to describing the major characteristic morphological parameters for the identification of the critical transition points for tumor-cell spheroids in a collagen fiber scaffold. Results The system focuses on in vitro tumor modeling, e.g. the development of tumor-cell spheroids in a collagen fiber scaffold and the monitoring of cell transition from proliferation to invasion. By applying this approach to multiple tumor spheroid models, such as U87 (glioma tumor), H1299 (lung cancer), and MDA-MB-231 (breast cancer) cells, we have obtained quantitative morphological references to evaluate the proliferation-to-invasion transition time, as well as differentiating the invasion potential of tumor cells upon environmental changes, i.e. drug application. Conclusions Our quantitative approach provides a feasible clarification for the proliferation-to-invasion transition of in vitro tumor models (spheroids). Moreover, the transition time is a useful reference for the invasive potential of tumor cells. General significance This quantitative approach is potentially applicable to primary tumor cells, and thus has potential applications in the fields of cancer metastasis investigations and clinical diagnostics.

Exploring the complicated development of tumors and metastases needs a deep understanding of the physical and biological interactions between cancer cells and their surrounding microenvironments. One of the major challenges is the ability to mimic the complex 3-D tissue microenvironment that particularly influences cell proliferation, migration, invasion, and apoptosis in relation to the extracellular matrix (ECM). Traditional cell culture is unable to create 3-D cell scaffolds resembling tissue complexity and functions, and, in the past, many efforts were made to realize the goal of obtaining cell clusters in hydrogels. However, the available methods still lack a precise control of cell external microenvironments. Recently, the rapid development of microfabrication techniques, such as 3-D printing, microfluidics, and photochemistry, has offered great advantages in reconstructing 3-D controllable cancer cell microenvironments in vitro. Consequently, various biofunctionalized hydrogels have become the ideal candidates to help the researchers acquire some new insights into various diseases. Our review will discuss some important studies and the latest progress regarding the above approaches for the production of 3-D ECM structures for cancer and other diseases. Especially, we will focus on new discoveries regarding the impact of the ECM on different aspects of cancer metastasis, e.g., collective invasion, enhanced intravasation by stress and aligned collagen fibers, angiogenesis regulation, as well as on drug screening.

Three-dimensional (3D) collective cell migration in a collagen-based extracellular matrix (ECM) is among one of the most significant topics in developmental biology, cancer progression, tissue regeneration, and immune response. Recent studies have suggested that collagen-fiber mediated force transmission in cellularized ECM plays an important role in stress homeostasis and regulation of collective cellular behaviors. Motivated by the recent in vitro observation that oriented collagen can significantly enhance the penetration of migrating breast cancer cells into dense Matrigel which mimics the intravasation process in vivo [Han et al. Proc. Natl. Acad. Sci. USA 113, 11208 (2016)PNASA60027-842410.1073/pnas.1610347113], we devise a procedure for generating realizations of highly heterogeneous 3D collagen networks with prescribed microstructural statistics via stochastic optimization. Specifically, a collagen network is represented via the graph (node-bond) model and the microstructural statistics considered include the cross-link (node) density, valence distribution, fiber (bond) length distribution, as well as fiber orientation distribution. An optimization problem is formulated in which the objective function is defined as the squared difference between a set of target microstructural statistics and the corresponding statistics for the simulated network. Simulated annealing is employed to solve the optimization problem by evolving an initial network via random perturbations to generate realizations of homogeneous networks with randomly oriented fibers, homogeneous networks with aligned fibers, heterogeneous networks with a continuous variation of fiber orientation along a prescribed direction, as well as a binary system containing a collagen region with aligned fibers and a dense Matrigel region with randomly oriented fibers. The generation and propagation of active forces in the simulated networks due to polarized contraction of an embedded ellipsoidal cell and a small group of cells are analyzed by considering a nonlinear fiber model incorporating strain hardening upon large stretching and buckling upon compression. Our analysis shows that oriented fibers can significantly enhance long-range force transmission in the network. Moreover, in the oriented-collagen-Matrigel system, the forces generated by a polarized cell in collagen can penetrate deeply into the Matrigel region. The stressed Matrigel fibers could provide contact guidance for the migrating cell cells, and thus enhance their penetration into Matrigel. This suggests a possible mechanism for the observed enhanced intravasation by oriented collagen.

In this report, a novel method towards synthesis of two-layer sandwiched graphene@(Li0.893Fe0.036)Co(PO4) nanoparticles (SG@LFCPO) has been presented. In the approach, the sheet-like precursor, as the sacrificial template, and glucose molecules, as the carbon source, are the key factors involved in forming the specific morphology in which both top and bottom graphene sheets tightly envelop the (Li0.893Fe0.036)Co(PO4) nanoparticles, just like a sandwich. Owing to the combination of various favorable conditions, such as Fe doping, graphene coating and morphology design, the as-prepared SG@LFCPO displays very promising performance in terms of rate performance (discharge capacity of 85 mA h g−1 at 20 C), cyclability (coulombic efficiency of around 92.6%), stability (capacity retention of 94.6% after 100 cycles) and fast kinetics.

A 3-D microfluidic system consisting of microchamber arrays embedded in a collagen hydrogel with tuneable biochemical gradients that mimics the tumour microenvironment of mammary glands was constructed for the investigation on the interactions between invasive breast cancer cells and stromal cells. The hollow microchambers in collagen provide a very similar 3-D environment to that in vivo that regulates collective cellular dynamics and behaviour, while the microfluidic channels surrounding the collagen microchamber arrays allow one to impose complex concentration gradients of specific biological molecules or drugs. We found that breast epithelial cells (MCF-10A) seeded in the microchambers formed lumen-like structures similar to those in epithelial layers. When MCF-10A cells were co-cultured with invasive breast cancer cells (MDA-MB-231), the formation of lumen-like structures in the microchambers was inhibited, indicating the capability of cancer cells to disrupt the structures formed by surrounding cells for further invasion and metastasis. Subsequent mechanism studies showed that down regulation of E-cad expression due to MMPs produced by the cancer cells plays a dominant role in determining the cellular behaviour. Our microfluidic system offers a robust platform for high throughput studies that aim to understand combinatorial effects of multiple biochemical and microenvironmental factors.

Cancer cell motility and its heterogeneity play an important role in metastasis, which is responsible for death of 90% of cancer patients. Here, in combination with a microfluidic technique, single-cell tracking, and systematic motility analysis, we present a rapid and quantitative approach to judge the motility heterogeneity of breast cancer cells MDA-MB-231 and MCF-7 in a well-defined three-dimensional (3D) microenvironment with controllable conditions. Following this approach, identification of highly mobile active cells in a medium with epithelial growth factor will provide a practical tool for cell invasion and metastasis investigation of multiple cancer cell types, including primary cells. Further, this approach could potentially become a speedy (∼hours) and efficient tool for basic and clinical diagnosis.

Cadherins, a large family of calcium-dependent adhesion molecules, are critical for intercellular adhesion. While crystallographic structures for several cadherins show clear structural similarities, their relevant adhesive strengths vary and their mechanisms of adhesion between types I and II cadherin subfamilies are still unclear. Here, stretching of cadherins was explored experimentally by atomic force microscopy and computationally by steered molecular dynamics (SMD) simulations, where partial unfolding of the E-cadherin ectodomains was observed. The SMD simulations on strand-swapping cadherin dimers displayed similarity in binding strength, suggesting contributions of other mechanisms to explain the strength differences of cell adhesion in vivo. Systematic simulations on the unfolding of the extracellular domains of type I and II cadherins revealed diverse pathways. However, at the earliest stage, a remarkable similarity in unfolding was observed for the various type I cadherins that was distinct from that for type II cadherins. This likely correlates positively with their distinct adhesive properties, suggesting that the initial forced deformation in type I cadherins may be involved in cadherin-mediated adhesion. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:25

Development of an in vitro three-dimensional (3D) model that closely mimics actual environment of tissue has become extraordinarily important for anti-cancer study. In recent years, various 3D cell culture systems have been developed, with multicellular tumor spheroids being the most popular and effective model. In this work, we present a microfluidic device used as a robust platform for generating core–shell hydrogel microspheres with precisely controlled sizes and varied components of hydrogel matrix. To gain a better understanding of the governing mechanism of microsphere formation, computational models based on multiphase flow were developed to numerically model the droplet generation and velocity field evolution process with COMSOL Multiphysics software. Our modeling results show good agreement with experiments in size dependence on flow rate as well as effect of vortex flow on microsphere formation. With real-time tuning of the flow rates of aqueous phase and oil phase, tumor cells were encapsulated into the microspheres with controllable core–shell structure and different volume ratios of core (comprised of alginate, Matrigel, and/or Collagen) and shell (comprised of alginate). Viability of cells in four different hydrogel matrices were evaluated by standard acridine orange (AO) and propidium iodide (PI) staining. The proposed microfluidic system can play an important role in engineering the in vitro micro-environment of tumor spheroids to better mimic the actual in vivo 3D spatial structure of a tumor and perfect the 3D tumor models for more effective clinical therapies.

A systematic understanding of the evolution and growth dynamics of invasive solid tumors in response to different chemotherapy strategies is crucial for the development of individually optimized oncotherapy. Here, we develop a hybrid three-dimensional (3D) computational model that integrates pharmacokinetic model, continuum diffusion-reaction model and discrete cell automaton model to investigate 3D invasive solid tumor growth in heterogeneous microenvironment under chemotherapy. Specifically, we consider the effects of heterogeneous environment on drug diffusion, tumor growth, invasion and the drug-tumor interaction on individual cell level. We employ the hybrid model to investigate the evolution and growth dynamics of avascular invasive solid tumors under different chemotherapy strategies. Our simulations reproduce the well-established observation that constant dosing is generally more effective in suppressing primary tumor growth than periodic dosing, due to the resulting continuous high drug concentration. In highly heterogeneous microenvironment, the malignancy of the tumor is significantly enhanced, leading to inefficiency of chemotherapies. The effects of geometrically-confined microenvironment and non-uniform drug dosing are also investigated. Our computational model, when supplemented with sufficient clinical data, could eventually lead to the development of efficient in silico tools for prognosis and treatment strategy optimization., Comment: 41 pages, 8 figures

Perovskite solar cells (PSCs) have been intensively investigated over the last several years. Unprecedented progress has been made in improving their power conversion efficiency; however, the stability of perovskite materials and devices remains a major obstacle for the future commercialization of PSCs. In this review, recent progress in PSCs is summarized in terms of the hybridization of compositions and device architectures for PSCs, with special attention paid to device stability. A brief history of the development of PSCs is given, and their chemical structures, optoelectronic properties, and the different types of device architectures are discussed. Then, perovskite composition engineering is reviewed in detail, with particular emphasis on the cationic components and their impact on film morphology, the optoelectronic properties, device performance, and stability. In addition, the impact of two-dimensional and/or one-dimensional and nanostructured perovskites on structural and device stability is surveyed. Finally, a future outlook is proposed for potential resolutions to overcome the current issues.

We report Atomic Force Microscopy (AFM) and Scanning Kelvin Probe Microscopy (SKPM) studies on the surface morphology and surface potential properties of CH3NH3PbI3, CH3NH3PbI3-xClx, CH3NH3PbI3-xBrx and CH3NH3PbBr3-xClx, respectively. For CH3NH3PbI3 rod structure, its surface potential is independent of the precursor concentration, suggesting a robust electronic feature. Surface potential studies of CH3NH3PbI3 particle reveal that the Fermi level within CH3NH3PbI3 is strongly influenced by the substrate. In the case of CH3NH3PbI3-xClx, its surface potential depends on precursor concentrations and we suspect that chlorine concentrated solutions might lead to more chlorine incorporation in the final products, thus lowering its Fermi level. Also, we studied the surface potentials of CH3NH3PbI3-xBrx and CH3NH3PbBr3-xClxwith specified halide ratios. The surface potential differences between different samples are related to their work function variations. These results are helpful to the understanding of the structural and electronic properties of perovskite materials.

Increasing the triboelectric charge density on the friction layer of polydimethylsiloxane (PDMS) is a basic approach towards improving the output performance of a triboelectric nanogenerator (TENG). Most previous work focuses on the surface structure or dielectric properties, nonetheless, a few studies have focused on electronegative modification. NaNbO3-PDMS TENG (N-TENG) devices are fabricated by dispersing cubic NaNbO3, which is a lead-free piezoelectric material with molecular oxygen dangling bonds on the surface of the crystal, into the PDMS at different mass ratios. When the mass ratio is 7 wt%, the maximum output performance of the N-TENG is obtained. The open-circuit voltage is 550 V, the short-circuit current is 16 µA, and the effective power densities reach up to 5.5 W m−2 at a load resistance of ~100 MΩ. The N-TENG has been used to assemble self-powered electronic watches and illuminate commercial light-emitting diodes, respectively. Its fundamental mechanism has also been discussed in detail from the perspective of dielectric modulation and electronegative modification. This N-TENG technology is revealed to be a splendid candidate for application in large-scale device fabrication, flexible sensors and biological devices thanks to its easy fabrication process, low consumption, high output power density and biocompatibility.

Though having attracted extensive interests as the substitution for dye-sensitized TiO2 solar cell, hybrid nanocomposites of conducting polymer, and inorganic semiconductors for solar cells have still gave much less conversion efficiency. The photovoltaic processes are expected to take place mainly near the heterogeneous interfaces but directly visualizing those processes and correlating them with local nanostructures have not been established yet. Such a relationship is very important for the improvement of structural designs of the hybrid systems with better conversion efficiencies. In this article, two advanced microscopic techniques, near-field scanning optical microscopy, and scanning electrostatic potential microscopy are employed to explore the photoinduced charge separation processes and kinetics in nanocomposites of poly(1,4-phenylenevinylene) and TiO2 nanoparticles, as well as their association with the local nanostructures. The results suggest that charge separation can be the dominant pathway ...

The mechanism by which light is converted into chemical energy in a natural photosynthetic system has drawn considerable research interest. Using fluorescence spectroscopy and microscopic imaging, ...

Cadherin-mediated adhesion plays a crucial role in multicellular organisms. Dysfunction within this adhesion system has major consequences in many pathologies, including cancer invasion and metastasis. However, mechanisms controlling cadherin recognition and adhesive strengthening are only partially understood. Here, we investigated the homophilic interactions and mechanical stability of the extracellular (EC) domains of E-cadherin and cadherin 7 using atomic force microscopy and magnetic tweezers. Besides exhibiting stronger interactions, E-cadherin also showed more efficient force-induced self-strengthening of interactions than cadherin 7. In addition, the distributions of the unbinding forces for both cadherins partially overlap with those of the unfolding forces, indicating that partial unfolding/deformation of the cadherin EC domains may take place during their homophilic interactions. These conformational changes may be involved in cadherins physiology function and contribute to the significant differences in adhesive strength mediated by type I and type II cadherins.

Nature Communications 5: Article number: 4525 (2014); Published: 31 July 2014; Updated: 4 March 2015 The affiliation details for Jie Yan are incorrect in this Article. The correct affiliation details for this author are given below: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.

Quantum chemical calculations and experiments on model compounds are used to study the effect of conformational changes on intramolecular electron transfer in perylenebisimide–biphenyl dyads. The molecular orbital energy level of the biphenyl moiety and thus the free energy change for electron transfer depends on the dihedral angle between the two phenyl rings. Dramatic changes in the orbital energy levels result in very different electron transfer behavior for three model compounds. These changes are accurately predicted by calculations using density functional theory, which also give accurate results for geometries, suggesting such calculations can be useful in designing molecular electronic species.

It is widely appreciated that single-molecule spectroscopy (SMS) can be used to measure properties of individual molecules which would normally be obscured in an ensemble-averaged measurement. In this report we show how SMS can be used to measure photoinduced interfacial electron transfer (IET) and back electron transfer rates in a prototypical chromophore-bridge-electrode nonadiabatic electron transfer system. N-(1-hexylheptyl)-N'-(12-carboxylicdodecyl)perylene-3,4,9,10-tetracarboxylbisimide was synthesized and incorporated into mixed self-assembled monolayers (SAMs) on an ITO (tin-doped indium oxide, a p-type semiconductor) electrode. Single-molecule fluorescence time trajectories from this system reveals "blinks", momentary losses in fluorescence (>20 ms to seconds in duration), which are attributed to discrete electron transfer events: electron injection from the perylene chromophore into the conduction band of the ITO leads to the loss of fluorescence, and charge recombination (back electron transfer) leads to the return of fluorescence. Such blinks are not observed when an electrode is not present. The fluorescence trajectories were analyzed to obtain the forward and back electron rates; the measured rates are found to lie in the millisecond to second regime. Different rates are observed for different molecules, but the lifetime distributions for the forward or back electron transfer for any given molecule are well fit by single exponential kinetics. The methodology used is applicable to a wide variety of systems and can be used to study the effects of distance, orientation, linker, environment, etc. on electron transfer rates. The results and methodology have implications for molecular electronics, where understanding and controlling the range of possible behaviors inherent to molecular systems will likely be as important as understanding the individual behavior of any given molecule.

It is widely appreciated that single-molecule spectroscopy (SMS) can be used to measure properties of individual molecules which would normally be obscured in an ensemble-averaged measurement. In this article, we show how SMS can be used to investigate intramolecular electron transfer (IET) processes in model dimer systems composed of two perylene chromophores connected via an adjustable bridge. The fluorescence behaviors of a large number of molecules are cataloged and the results statistically analyzed to gauge information about the range of behaviors of the ensemble. Single-molecule fluorescence time trajectories reveal “blinks”, momentary losses in fluorescence (>20 ms to seconds in duration), which are attributed to discrete IET excursions to the charge-separated (CS) state. We find that fluorescence blinking behavior is dependent on bridge length and chromophore geometry, which affect the electronic coupling and therefore the IET. The statistical trends observed in this analysis are used to corrobor...

Preferred-orientated 4H–SiC nanocrystalline films on silicon substrates were successfully prepared by the pyrolysis of the polyimide Langmuir–Blodgett films containing nanometer-sized amorphous silicon nitride powders. Fourier-transform infrared spectra revealed 4H–SiC nanoparticles with interfacial silicon oxide. Ultraviolet photoluminescence with energies above the band gap of bulk 4H–SiC was observed from the films in which the mean size of 4H–SiC particles was 10 nm, while no photoluminescence was observed from the films in which the mean size of particles was 17 nm. A quantum confinement/luminescence center model is suggested to explain the origin of the ultraviolet luminescence.

Plasmon-driven surface catalytic (PDSC) reaction in Ag/Au nanoparticle monomer or dimer-film gaps are experimentally and theoretically investigated, using surface enhanced Raman scattering (SERS) and finite element method. The variation of SERS spectra in different nano gaps of nanoparticle-film systems indicated the PDSC reaction was largely depended on the number of nanoparticles. The higher Raman intensity of p, p'-dimercaptoazobenzene (DMAB) in dimer-film nanogap was because effective coupling of induced image charge on metal film in hybridized plasmonic gap mode, which was confirmed by the electric field distribution. Furthermore, the influence of material and wavelength was also studied to obtain the optimal experimental condition for best surface catalysis in hybridized plasmonic gap mode. Our studies in this common configuration of plasmonic nanostructure are of great significance not only in the field of catalysis on metal surface but also in other surface plasmon fields such as senor, photon detection, water splitting, etc.

Mechanical stretch-induced tyrosine phosphorylation in the proline-rich 306-residue substrate domain (CasSD) of p130Cas (or BCAR1) has eluded an experimentally validated structural understanding. Cellular p130Cas tyrosine phosphorylation is shown to function in areas without internal actomyosin contractility, sensing force at the leading edge of cell migration. Circular dichroism shows CasSD is intrinsically disordered with dominant polyproline type II conformations. Strongly conserved in placental mammals, the proline-rich sequence exhibits a pseudo-repeat unit with variation hotspots 2–9 residues before substrate tyrosine residues. Atomic-force microscopy pulling experiments show CasSD requires minimal extension force and exhibits infrequent, random regions of weak stability. Proteolysis, light scattering and ultracentrifugation results show that a monomeric intrinsically disordered form persists for CasSD in solution with an expanded hydrodynamic radius. All-atom 3D conformer sampling with the TraDES package yields ensembles in agreement with experiment when coil-biased sampling is used, matching the experimental radius of gyration. Increasing β-sampling propensities increases the number of prolate conformers. Combining the results, we conclude that CasSD has no stable compact structure and is unlikely to efficiently autoinhibit phosphorylation. Taking into consideration the structural propensity of CasSD and the fact that it is known to bind to LIM domains, we propose a model of how CasSD and LIM domain family of transcription factor proteins may function together to regulate phosphorylation of CasSD and effect machanosensing., Author Summary Mechanical stretching of cells causes the substrate domain of p130Cas (CasSD) to be phosphorylated on 15 tyrosine residues embedded along its length. CasSD is rich in proline and surprisingly well conserved in placental mammals. Stretching of CasSD by atomic force microscopy has identified that it requires far less force than normal folded proteins. Classical biophysical analyses have determined that CasSD is a typical intrinsically disordered protein, a difficult-to-study group of molecules covering about 30% of human proteins. The average size of CasSD is larger and elongated than folded globular proteins but smaller than chemically denatured proteins. We have simulated a large number of all-atom protein structures using a fast all-atom sampling method. The result is in good agreement with the experimental observation. As it is already known that stretching somehow exposes the tyrosine residues to phosphorylation, a mechanism is proposed where straightening of the p130Cas substrate domain backbone conformation through mechanical stretching can lead to dissociation of p130Cas-binding LIM domain proteins and exposure of CasSD tyrosine residues for phosphorylation. This study has led to a new model of a protein-based mechanism of force sensing at the leading edge of cells that allows the cells to feel their way as they move.

Force sensing at cadherin-mediated adhesions is critical for their proper function. α-Catenin, which links cadherins to actomyosin, has a crucial role in this mechanosensing process. It has been hypothesized that force promotes vinculin binding, although this has never been demonstrated. X-ray structure further suggests that α-catenin adopts a stable auto-inhibitory conformation that makes the vinculin-binding site inaccessible. Here, by stretching single α-catenin molecules using magnetic tweezers, we show that the subdomains MI vinculin-binding domain (VBD) to MIII unfold in three characteristic steps: a reversible step at ~5 pN and two non-equilibrium steps at 10-15 pN. 5 pN unfolding forces trigger vinculin binding to the MI domain in a 1:1 ratio with nanomolar affinity, preventing MI domain refolding after force is released. Our findings demonstrate that physiologically relevant forces reversibly unfurl α-catenin, activating vinculin binding, which then stabilizes α-catenin in its open conformation, transforming force into a sustainable biochemical signal.