Ultra-Stretchable Spiral Hybrid Conductive Fiber with 500%-Strain Electric Stability and Deformation-Independent Linear Temperature Response.

Stretchable configuration occupies priority in devising flexible conductors used in intelligent electronics and implantable sensors. While most conductive configurations cannot suppress electrical variations against extreme deformation and ignore inherent material characteristics. Herein, a spiral hybrid conductive fiber (SHCF) composed of aramid polymeric matrix and silver nanowires (AgNWs) coating is fabricated through shaping and dipping processes. The homochiral coiled configuration mimicked by plant tendrils not only enables its high elongation (958%), but also generates a superior deformation-insensitive effect to existing stretchable conductors. The resistance of SHCF maintains remarkable stability against extreme strain (500%), impact damage, air exposure (90 days), and cyclic bending (150 000 times). Moreover, the thermal-induced densification of AgNWs on SHCF achieves precise and linear temperature response toward a broad range (-20 to 100 °C). Its sensitivity further manifests high independence to tensile strain (0%-500%), allowing for flexible temperature monitoring of curved objects. Such unique strain-tolerant electrical stability and thermosensation hold broad prospects for SHCF in lossless power transferring and expeditious thermal analysis.

Multi-scale simulation of early kidney branching morphogenesis.

An important feature of the branch morphogenesis during kidney development is the termination of the tips on the outer surface of a kidney. This feature requires the avoidance of the intersection between the tips and existing ducts inside the kidney. Here, we started from a continuous model and implemented the coarse grained rules into a fast and discrete simulations. The ligand-receptor-based Turing mechanism suggests a repulsion that decreases exponentially with distance between interacting branches, preventing the intersection between neighboring branches. We considered this repulsive effect in numerical simulations and successfully reproduce the key features of the experimentally observed branch morphology for an E15.5 kidney. We examine the similarity of several geometrical parameters between the simulation results and experimental observations. The good agreement between the simulations and experiments suggests that the concentration decay caused by the absorption of glial cell line derived neurotrophic factor might be the key factor to affect the geometry in early kidney development.

A Novel Reconstruction Method for Measurement Data Based on MTLS Algorithm.

Reconstruction methods for discrete data, such as the Moving Least Squares (MLS) and Moving Total Least Squares (MTLS), have made a great many achievements with the progress of modern industrial technology. Although the MLS and MTLS have good approximation accuracy, neither of these two approaches are robust model reconstruction methods and the outliers in the data cannot be processed effectively as the construction principle results in distorted local approximation. This paper proposes an improved method that is called the Moving Total Least Trimmed Squares (MTLTS) to achieve more accurate and robust estimations. By applying the Total Least Trimmed Squares (TLTS) method to the orthogonal construction way in the proposed MTLTS, the outliers as well as the random errors of all variables that exist in the measurement data can be effectively suppressed. The results of the numerical simulation and measurement experiment show that the proposed algorithm is superior to the MTLS and MLS method from the perspective of robustness and accuracy.

Self-Assembly of Stable Nanoscale Platelets from Designed Elastin-like Peptide-Collagen-like Peptide Bioconjugates.

The self-assembly of nanostructures from elastin-like (poly)peptide (ELP) containing block copolymers has been a subject of intense investigation over decades. However, short synthetic ELPs have rarely been used due to their high inverse transition temperature; the use of short ELPs has largely been limited to polymer conjugates. Motivated by our previous work which successfully overcame this barrier by simply conjugating short ELPs with a triple-helix-forming collagen-like peptide, in this study, we further extend the ELP library to a series of ELPs equipped with aromatic residues and having sequences as short as four pentapeptide motifs. The resulting elastin-like peptide-collagen-like peptide (ELP-CLP) bioconjugates unexpectedly self-assembled into nanosized platelets likely by forming a bilayer structure. Given the previously demonstrated ability of many other CLP conjugates to target collagens and the potential for encapsulation of hydrophobic drugs in collapsed ELPs, these ELP-CLP nanoplatelets may offer similar opportunities for targeted delivery in biomedical and other arenas.

Manipulation of Glutathione-Mediated Degradation of Thiol-Maleimide Conjugates.

The retro Michael-type addition and thiol exchange of thioether succinimide click linkages in response to thiol-containing environments offers a novel strategy for the design of glutathione-sensitive degradable hydrogels for controlled drug delivery. Here we characterize the kinetics and extent of the retro Michael-type addition and thiol exchange with changes in both the p Ka of the thiols and the identity of N-substituents of maleimides. A series of N-substituted thioether succinimides were prepared through typical Michael-type addition. Model studies (1H NMR, HPLC) of 4-mercaptophenylacetic acid (MPA, p Ka 6.6) conjugated to N-ethyl maleimide (NEM), N-phenyl maleimide (NPM), or N-aminoethyl maleimide (NAEM) and then incubated with glutathione showed half-lives of conversion from 3.1 to 18 h, with extents of conversion from approximately 12% to 90%. The variations in the rates of exchange and hydrolytic ring opening appear to be mediated by resonance effects, electron-withdrawing capacity of the N-substituted moiety, as well as the potential for intramolecular catalytic hydrogen bonding of amine substituents with water (particularly in the case of ring opening). Further model studies of 4-mercaptohydrocinnamic acid (MPP, p Ka 7.0) and N-acetyl-l-cysteine (NAC, p Ka 9.5) conjugated to selected N-substituted maleimides and then incubated with glutathione showed half-lives of conversion from 3.6 to 258 h, with extents of conversion from approximately 1% to 90%. A higher p Ka of the thiol decreased the rate of the exchange reaction and limited the impact of other electronic effects of N-substituents on the extents of conversion. Additional factors affecting the conversion kinetics were studied on NEM conjugates. The kinetics of the retro Michael-type addition and exchange reaction were not hindered by thiol traps of lower p Ka, but were retarded in conditions of lower pH. These studies shed light into details of thiol and maleimide design that could be used to tune the rates of degradation of drug and polymer conjugates for a variety of applications.

Collagen-Like Peptide Bioconjugates.

Collagen-like peptides (CLPs), also known as collagen-mimetic peptides (CMPs), are short synthetic peptides that mimic the triple helical conformation of native collagens. Traditionally, CLPs have been widely used in deciphering the chemical basis for collagen triple helix stabilization, mimicking collagen fibril formation and fabricating other higher-order supramolecular self-assemblies. While CLPs have been used extensively for elucidation of the assembly of native collagens, less work has been reported on the use of CLP-polymer and CLP-peptide conjugates in the production of responsive assemblies. CLP triple helices have been used as physical cross-links in CLP-polymer hydrogels with predesigned thermoresponsiveness. The more recently reported ability of CLP to target native collagens via triple helix hybridization has further inspired the production of CLP-polymer and CLP-peptide bioconjugates and the employment of these conjugates in generating well-defined nanostructures for targeting collagen substrates. This review summarizes the current progress and potential of using CLPs in biomedical arenas and is intended to serve as a general guide for designing CLP-containing biomaterials.

Thermoresponsive Elastin-b-Collagen-Like Peptide Bioconjugate Nanovesicles for Targeted Drug Delivery to Collagen-Containing Matrices.

Over the past few decades, (poly)peptide block copolymers have been widely employed in generating well-defined nanostructures as vehicles for targeted drug delivery applications. We previously reported the assembly of thermoresponsive nanoscale vesicles from an elastin-b-collagen-like peptide (ELP-CLP). The vesicles were observed to dissociate at elevated temperatures, despite the LCST-like behavior of the tethered ELP domain, which is suggested to be triggered by the unfolding of the CLP domain. Here, the potential of using the vesicles as drug delivery vehicles for targeting collagen-containing matrices is evaluated. The sustained release of an encapsulated model drug was achieved over a period of 3 weeks, following which complete release could be triggered via heating. The ELP-CLP vesicles show strong retention on a collagen substrate, presumably through collagen triple helix interactions. Cell viability and proliferation studies using fibroblasts and chondrocytes suggest that the vesicles are highly cytocompatible. Additionally, essentially no activation of a macrophage-like cell line is observed, suggesting that the vesicles do not initiate an inflammatory response. Endowed with thermally controlled delivery, the ability to bind collagen, and excellent cytocompatibility, these ELP-CLP nanovesicles are suggested to have significant potential in the controlled delivery of drugs to collagen-containing matrices and tissues.

Yes-associated protein impacts adherens junction assembly through regulating actin cytoskeleton organization.

The Hippo pathway effector Yes-associated protein (YAP) regulates liver size by promoting cell proliferation and inhibiting apoptosis. However, recent in vivo studies suggest that YAP has important cellular functions other than controlling proliferation and apoptosis. Transgenic YAP expression in mouse hepatocytes results in severe jaundice. A possible explanation for the jaundice could be defects in adherens junctions that prevent bile from leaking into the blood stream. Indeed, immunostaining of E-cadherin and electron microscopic examination of bile canaliculi of Yap transgenic livers revealed abnormal adherens junction structures. Using primary hepatocytes from Yap transgenic livers and Yap knockout livers, we found that YAP antagonizes E-cadherin-mediated cell-cell junction assembly by regulating the cellular actin architecture, including its mechanical properties (elasticity and cortical tension). Mechanistically, we found that YAP promoted contractile actin structure formation by upregulating nonmuscle myosin light chain expression and cellular ATP generation. Thus, by modulating actomyosin organization, YAP may influence many actomyosin-dependent cellular characteristics, including adhesion, membrane protrusion, spreading, morphology, and cortical tension and elasticity, which in turn determine cell differentiation and tissue morphogenesis.

Noncovalent Modulation of the Inverse Temperature Transition and Self-Assembly of Elastin-b-Collagen-like Peptide Bioconjugates.

Stimuli-responsive nanostructures produced with peptide domains from the extracellular matrix offer great opportunities for imaging and drug delivery. Although the individual utility of elastin-like (poly)peptides and collagen-like peptides in such applications has been demonstrated, the synergistic advantages of combining these motifs in short peptide conjugates have surprisingly not been reported. Here, we introduce the conjugation of a thermoresponsive elastin-like peptide (ELP) with a triple-helix-forming collagen-like peptide (CLP) to yield ELP-CLP conjugates that show a remarkable reduction in the inverse transition temperature of the ELP domain upon formation of the CLP triple helix. The lower transition temperature of the conjugate enables the facile formation of well-defined vesicles at physiological temperature and the unexpected resolubilization of the vesicles at elevated temperatures upon unfolding of the CLP domain. Given the demonstrated ability of CLPs to modify collagens, our results not only provide a simple and versatile avenue for controlling the inverse transition behavior of ELPs, but also suggest future opportunities for these thermoresponsive nanostructures in biologically relevant environments.

Temperature-triggered phase separation of a hydrophilic resilin-like polypeptide.

Temperature-triggered phase separation of recombinant proteins has offered substantial opportunities in the design of nanoparticles for a variety of applications. Herein, the temperature-triggered phase separation behavior of a recombinant hydrophilic resilin-like polypeptide (RLP) is described. The transition temperature and sizes of RLP-based nanoparticles can be modulated based on variations in polypeptide concentration, salt identity, ionic strength, pH, and denaturing agents, as indicated via UV-Vis spectroscopy and dynamic light scattering (DLS). The irreversible particle formation is coupled with secondary conformational changes from a random coil conformation to a more ordered ß-sheet structure. These RLP-based nanoparticles could find potential use as mechanically-responsive components in drug delivery, nanospring, nanotransducer, and biosensor applications.

Molecular mechanisms of cellular mechanosensing.

Mechanical forces direct a host of cellular and tissue processes. Although much emphasis has been placed on cell-adhesion complexes as force sensors, the forces must nevertheless be transmitted through the cortical cytoskeleton. Yet how the actin cortex senses and transmits forces and how cytoskeletal proteins interact in response to the forces is poorly understood. Here, by combining molecular and mechanical experimental perturbations with theoretical multiscale modelling, we decipher cortical mechanosensing from molecular to cellular scales. We show that forces are shared between myosin II and different actin crosslinkers, with myosin having potentiating or inhibitory effects on certain crosslinkers. Different types of cell deformation elicit distinct responses, with myosin and α-actinin responding to dilation, and filamin mainly reacting to shear. Our observations show that the accumulation kinetics of each protein may be explained by its molecular mechanisms, and that protein accumulation and the cell's viscoelastic state can explain cell contraction against mechanical load.

Collagen-like peptides and peptide-polymer conjugates in the design of assembled materials.

Collagen is the most abundant protein in mammals, and there has been long-standing interest in understanding and controlling collagen assembly in the design of new materials. Collagen-like peptides (CLP), also known as collagen-mimetic peptides (CMP) or collagen-related peptides (CRP), have thus been widely used to elucidate collagen triple helix structure as well as to produce higher-order structures that mimic natural collagen fibers. This mini-review provides an overview of recent progress on these topics, in three broad topical areas. The first focuses on reported developments in deciphering the chemical basis for collagen triple helix stabilization, which we review not with the intent of describing the basic structure and biological function of collagen, but to summarize different pathways for designing collagen-like peptides with high thermostability. Various approaches for producing higher-order structures via CLP self-assembly, via various types of intermolecular interaction, are then discussed. Finally, recent developments in a new area, the production of polymer-CLP bioconjugates, are summarized. Biological applications of collagen contained hydrogels are also included in this section. The topics may serve as a guide for the design of collagen-like peptides and their bioconjugates for targeted application in the biomedical arena.

A glomerulus chip with spherically twisted cell-laden hollow fibers as glomerular capillary tufts.

Glomerulus-on-a-chip, as a promising alternative for drug nephrotoxicity evaluation, is attracting increasing attention. For glomerulus-on-a-chip, the more biomimetic the chip is, the more convincing the application of the chip is. In this study, we proposed a hollow fiber-based biomimetic glomerulus chip that can regulate filtration in response to blood pressure and hormone levels. On the chip developed here, bundles of hollow fibers were spherically twisted and embedded in designed Bowman's capsules to form spherical glomerular capillary tufts, with podocytes and endotheliocytes cultured on the outer and inner surfaces of the hollow fibers, respectively. We evaluated the morphology of cells, the viability of cells, and the metabolic function of cells in terms of glucose consumption and urea synthesis by comparing the results obtained under fluidic and static conditions, confirmed the barrier function of the endotheliocyte-fiber membrane-podocyte structure by monitoring the diffusion of fluorescein isothiocyanate (FITC)-labeled inulin, albumin and IgG, and, for the first time, achieved on-chip filtration regulation in response to the hormone atrial natriuretic peptide. In addition, the application of the chip in the evaluation of drug nephrotoxicity was also preliminarily demonstrated. This work offers insights into the design of a more physiologically similar glomerulus on a microfluidic chip.

Transport Channels of Air Pollutants Affecting the Southern Sichuan Basin Based on Gridded Dispersion Simulation.

Air pollutants suspended in the atmosphere have a large impact on air quality, climate, and human health. As one of the important populated and industrialized regions in China, the Sichuan Basin (SCB) has confronted severe air pollution in recent years. Previous studies have shown that regional transport played a significant role in the formation of regional pollution in the SCB, particularly in the southern basin. Using Yibin and Zigong as representative receptor cities, we further identified the transport channels affecting the southern basin by conducting gridded dispersion simulations. A total of seven channels were identified, including three for cyclonic transport, three through the mountainous areas between the Longquan Mountain and the Huaying Mountain, and one along the Yangtze River. Varying seasonal distributions of their occurrence frequencies were observed. Furthermore, observational evidence for several universal channels was presented during a typical transport case. The transport pathways identified in this study can guide the planning of regional distribution of emission sources and the measures for regional joint prevention and control of air pollution.

Wearable Safeguarding Leather Composite with Excellent Sensing, Thermal Management, and Electromagnetic Interference Shielding.

This work illustrates a "soft-toughness" coupling design method to integrate the shear stiffening gel (SSG), natural leather, and nonwoven fabrics (NWF) for preparing leather/MXene/SSG/NWF (LMSN) composite with high anti-impact protecting, piezoresistive sensing, electromagnetic interference (EMI) shielding, and human thermal management performance. Owing to the porous fiber structure of the leather, the MXene nanosheets can penetrate leather to construct a stable 3D conductive network; thus both the LM and LMSN composites exhibit superior conductivity, high Joule heating temperature, and an efficient EMI shielding effectiveness. Due to the excellent energy absorption of the SSG, the LMSN composites possess a huge force-buffering (about 65.5%), superior energy dissipation (above 50%), and a high limit penetration velocity of 91 m s-1 , showing extraordinary anti-impact performance. Interestingly, LMSN composites possess an unconventional opposite sensing behavior to piezoresistive sensing (resistance reduction) and impact stimulation (resistance growing), thus they can distinguish the low and high energy stimulus. Ultimately, a soft protective vest with thermal management and impact monitoring performance is further fabricated, and it shows a typical wireless impact-sensing performance. This method is expected to have broad application potential in the next-generation wearable electronic devices for human safeguarding.

Biogenic Copper Selenide Nanoparticles for Near-Infrared Photothermal Therapy Application.

Near-infrared (NIR) photothermal therapy (PTT) is attractive for cancer treatment but is currently restricted by limited availability and insufficient NIR-II photoactivity of photothermal agents, for which artificial nanomaterials are usually used. Here, we report the first use of biogenic nanomaterials for PTT application. A fine-controlled extracellular biosynthesis of copper selenide nanoparticles (bio-Cu2-xSe) by Shewanella oneidensis MR-1 was realized. The resulting bio-Cu2-xSe, with fine sizes (∼35.5 nm) and high product purity, exhibited 76.9% photothermal conversion efficiency under 1064 nm laser irradiation, outperforming almost all the existing counterparts. The protein capping also imparted good biocompatibility to bio-Cu2-xSe to favor a safe PTT application. The in vivo PTT with injected bio-Cu2-xSe in mice (without extraction nor further modification) showed 87% tumor ablation without impairing the normal organisms. Our work not only opens a green route to synthesize the NIR-II photothermal nanomaterial but may also lay a basis for the development of bacteria-nanomaterial hybrid therapy technologies.

Understanding the cooperative interaction between myosin II and actin cross-linkers mediated by actin filaments during mechanosensation.

Myosin II is a central mechanoenzyme in a wide range of cellular morphogenic processes. Its cellular localization is dependent not only on signal transduction pathways, but also on mechanical stress. We suggest that this stress-dependent distribution is the result of both the force-dependent binding to actin filaments and cooperative interactions between bound myosin heads. By assuming that the binding of myosin heads induces and/or stabilizes local conformational changes in the actin filaments that enhances myosin II binding locally, we successfully simulate the cooperative binding of myosin to actin observed experimentally. In addition, we can interpret the cooperative interactions between myosin and actin cross-linking proteins observed in cellular mechanosensation, provided that a similar mechanism operates among different proteins. Finally, we present a model that couples cooperative interactions to the assembly dynamics of myosin bipolar thick filaments and that accounts for the transient behaviors of the myosin II accumulation during mechanosensation. This mechanism is likely to be general for a range of myosin II-dependent cellular mechanosensory processes.

Cytokinesis through biochemical-mechanical feedback loops.

Cytokinesis is emerging as a control system defined by interacting biochemical and mechanical modules, which form a system of feedback loops. This integrated system accounts for the regulation and kinetics of cytokinesis furrowing and demonstrates that cytokinesis is a whole-cell process in which the global and equatorial cortices and cytoplasm are active players in the system. Though originally defined in Dictyostelium, features of the control system are recognizable in other organisms, suggesting a universal mechanism for cytokinesis regulation and contractility.

Morphological transformations in a dually thermoresponsive coil-rod-coil bioconjugate.

We report the conformational and assembly behavior of a thermoresponsive triblock biohybrid conjugate under aqueous conditions. The triblock comprises of poly(diethylene glycol methyl ether methacrylate) (PDEGMEMA) conjugated to the ends of a triple-helix forming collagen-like peptide. The circular dichroism (CD) experiment confirms the ability of the collagen-like peptide middle block to assemble as a triple helix in the hybrid conjugate. Above the LCST (~35 °C), the collapse of the thermoresponsive PDEGMEMA polymer at the ends of the peptide domain resulted in a concomitant increase in the conformational stability of the peptide domain towards thermal denaturation. Upon cooling back, the kinetic conformational refolding behavior was still observed for the peptide domain in the hybrid conjugate. Static light scattering (SLS) experiments suggested the formation of supramolecular structures upon increasing solution temperatures to above the LCST. The scattering intensity increased with increasing temperature, until at 75 °C then it was found to decrease. Cryogenic scanning electron microscopy and regular transmission electron microscopy suggested the formation of spherical aggregates that increased in size with increasing temperature up to 65 °C and a morphological transformation into fibrils was also observed at 75 °C. The synergistic effect of dual thermoresponsive behavior from the peptide and the polymer block in the triblock hybrid is suggested for the observed conformational and assembly behaviors.

Effects of zinc oxide nanoparticles transformation in sulfur-containing water on its toxicity to microalgae: Physicochemical analysis, photosynthetic efficiency and potential mechanisms.

The environmental transformation of nanomaterials will have a significant impact on their ecotoxicity. Sulfidation process is one of the most important transformation processes in the aquatic environment. Although the sulfidation of ZnO nanoparticles (ZnO NPs) has been previously reported, the transformation characteristics and the relationship between the transformation process and toxicity mechanism to aquatic organisms, especially microalgae, require further study. Therefore, we systematically investigated the transformation properties of ZnO NPs in sulfur-containing water and its impact on the toxicity to microalgae. The results showed that the transformation products of ZnO NPs mainly contained ZnS nanoparticles, and their contents increased with the increase of sulfur-zinc molar ratio in the aqueous solution. After the first week of treatment, the sulfidized ZnO NPs showed less toxicity to microalgae than the pristine ZnO NPs, and interestingly, they exhibited higher toxicity over time. The zinc ions and transformation products played a major role in different treatment periods, resulting in different toxicity. The results of photosynthetic pigments, photosynthetic efficiency, and the relative electron transport rates indicated that the sulfidation process of ZnO NPs had a remarkable influence on algal photosynthesis. These newly acquired results will help us explore the transformation characteristics of ZnO NPs and reasonably assess their potential risks in the aquatic environment.