Measuring Heat Dissipation and Entropic Potential in Battery Cathodes Made with Conjugated and Conventional Polymer Binders Using Operando Calorimetry.

This study explores the influence of electronic and ionic conductivities on the behavior of conjugated polymer binders through the measurement of entropic potential and heat generation in an operating lithium-ion battery. Specifically, the traditional poly(vinylidene fluoride) (PVDF) binder in LiNi0.8Co0.15Al0.05O2 (NCA) cathode electrodes was replaced with semiconducting polymer binders based on poly(3,4-propylenedioxythiophene). Two conjugated polymers were explored: one is a homopolymer with all aliphatic side chains, and the other is a copolymer with both aliphatic and ethylene oxide side chains. We have shown previously that both polymers have high electronic conductivity in the potential range of NCA redox, but the copolymer has a higher ionic conductivity and a slightly lower electronic conductivity. Entropic potential measurements during battery cycling revealed consistent trends during delithiation for all of the binders, indicating that the binders did not modify the expected NCA solid solution deintercalation process. The entropic signature of polymer doping to form the conductive state could be clearly observed at potentials below NCA oxidation, however. Operando isothermal calorimetric measurements showed that the conductive binders resulted in less Joule heating compared to PVDF and that the net electrical energy was entirely dissipated as heat. In a comparison of the two conjugated polymer binders, the heat dissipation was lower for the homopolymer binder at lower C-rates, suggesting that electronic conductivity rather than ionic conductivity was the most important for reducing Joule heating at lower rates, but that ionic conductivity became more important at higher rates.

Control of Properties through Hydrogen Bonding Interactions in Conjugated Polymers.

Molecular design is crucial for endowing conjugated polymers (CPs) with unique properties and enhanced electronic performance. Introducing Hydrogen-bonding (H-bonding) into CPs has been a broadly exploited, yet still emerging strategy capable of tuning a range of properties encompassing solubility, crystallinity, electronic properties, solid-state morphology, and stability, as well as mechanical properties and self-healing properties. Different H-bonding groups can be utilized to tailor CPs properties based on the applications of interest. This review provides an overview of classes of H-bonding CPs (assorted by the different H-bond functional groups), the synthetic methods to introduce the corresponding H-bond functional groups and the impact of H-bonding in CPs on corresponding electronic and materials properties. Recent advances in addressing the trade-off between electronic performance and mechanical durability are also highlighted. Furthermore, insights into future directions and prospects for H-bonded CPs are discussed.

Relating Structure to Properties in Non-Conjugated Pendant Electroactive Polymers.

Non-conjugated pendant electroactive polymers (NCPEPs) are an emerging class of polymers that offer the potential of combining the desirable optoelectronic properties of conjugated polymers with the superior synthetic methodologies and stability of traditional non-conjugated polymers. Despite an increasing number of studies focused on NCPEPs, particularly on understanding fundamental structure-property relationships, no attempts have been made to provide an overview on established relationships to date. This review showcases selected reports on NCPEP homopolymers and copolymers that demonstrate how optical, electronic, and physical properties of the polymers are affected by tuning of key structural variables such as the chemical structure of the polymer backbone, molecular weight, tacticity, spacer length, the nature of the pendant group, and in the case of copolymers the ratios between different comonomers and between individual polymer blocks. Correlation of structural features with improved π-stacking and enhanced charge carrier mobility serve as the primary figures of merit in evaluating impact on NCPEP properties. While this review is not intended to serve as a comprehensive summary of all reports on tuning of structural parameters in NCPEPs, it highlights relevant established structure-property relationships that can serve as a guideline for more targeted design of novel NCPEPs in the future.

Room Temperature Synthesis of a Well-Defined Conjugated Polymer Using Direct Arylation Polymerization (DArP).

While a major improvement to the sustainability of conjugated polymer synthesis, traditional direct arylation polymerization (DArP) still requires high temperatures (typically >100 °C), necessitating a significant energy input requirement. Performing DArP at reduced or ambient temperatures would represent an improvement to the sustainability of the reaction. Here we describe the first report of a well-defined conjugated polymer synthesized by DArP at room temperature. Previous efforts toward room temperature DArP relied on the use of a near-stoichiometric silver reagent, an expensive coinage metal, which makes the reaction less cost-effective and sustainable. Here, room temperature polymerizations of 3,4-ethylenedioxythiophene (EDOT) and 9,9-dioctyl-2,7-diiodofluorene were optimized and provided molar mass (Mn) up to 11 kg/mol PEDOTF, and performing the reaction at the standard ambient temperature of 25 °C provided Mn up to 15 kg/mol. Model studies using other C-H monomers of varying electron density copolymerized with 9,9-dioctyl-2,7-diiodofluorene provided insight into the scope of the room temperature polymerization, suggesting that performing room temperature DArP is highly dependent on the electron richness of the C-H monomer.

High-Performance Intrinsically Stretchable Polymer Solar Cell with Record Efficiency and Stretchability Enabled by Thymine-Functionalized Terpolymer.

Designing new polymer semiconductors for intrinsically stretchable polymer solar cells (IS-PSCs) with high power conversion efficiency (PCE) and durability is critical for wearable electronics applications. Nearly all high-performance PSCs are constructed using fully conjugated polymer donors (PD) and small-molecule acceptors (SMA). However, a successful molecular design of PDs for high-performance and mechanically durable IS-PSCs without sacrificing conjugation has not been realized. In this study, we design a novel thymine side chain terminated 6,7-difluoro-quinoxaline (Q-Thy) monomer and synthesize a series of fully conjugated PDs (PM7-Thy5, PM7-Thy10, PM7-Thy20) featuring Q-Thy. The Q-Thy units capable of inducing dimerizable hydrogen bonding enable strong intermolecular PD assembly and highly efficient and mechanically robust PSCs. The PM7-Thy10:SMA blend demonstrates a combination of high PCE (>17%) in rigid devices and excellent stretchability (crack-onset value >13.5%). More importantly, PM7-Thy10-based IS-PSCs show an unprecedented combination of PCE (13.7%) and ultrahigh mechanical durability (maintaining 80% of initial PCE after 43% strain), illustrating the promising potential for commercialization in wearable applications.

Distinguishing between the Electrostatic Effects and Explicit Ion Interactions in a Stark Probe.

Vibrational Stark probes are incisive tools for measuring local electric fields in a wide range of chemical environments. The interpretation of the frequency shift often gets complicated due to the specific interactions of the probe, such as hydrogen bonding and Lewis bonding. Therefore, it is important to distinguish between the pure electrostatic response and the response due to such specific interactions. Here we report a molecular system that is sensitive to both the Stark effect from a single ion and the explicit Lewis bonding of ions with the probe. The molecule consists of a crown ether with an appended benzonitrile. The crown captures cations of various charges, and the electric field from the ions is sensed by the benzonitrile probe. Additionally, the lone pair of the benzonitrile can engage in Lewis interactions with some of the ions by donating partial charge density to the ions. Our system exhibits both of these effects and therefore is a suitable test bed for distinguishing between the pure electrostatic and the Lewis interactions. Our computational results show that the electrostatic influence of the ion is operative at large distances, while the Lewis interaction becomes important only within distances that permit orbital overlap. Our results may be useful for using the nitrile probe for measuring electrostatic and coordination effects in complex ionic environments such as the electrode-electrolyte interfaces.

Phase separation of Hippo signalling complexes.

The Hippo pathway was originally discovered to control tissue growth in Drosophila and includes the Hippo kinase (Hpo; MST1/2 in mammals), scaffold protein Salvador (Sav; SAV1 in mammals) and the Warts kinase (Wts; LATS1/2 in mammals). The Hpo kinase is activated by binding to Crumbs-Expanded (Crb-Ex) and/or Merlin-Kibra (Mer-Kib) proteins at the apical domain of epithelial cells. Here we show that activation of Hpo also involves the formation of supramolecular complexes with properties of a biomolecular condensate, including concentration dependence and sensitivity to starvation, macromolecular crowding, or 1,6-hexanediol treatment. Overexpressing Ex or Kib induces formation of micron-scale Hpo condensates in the cytoplasm, rather than at the apical membrane. Several Hippo pathway components contain unstructured low-complexity domains and purified Hpo-Sav complexes undergo phase separation in vitro. Formation of Hpo condensates is conserved in human cells. We propose that apical Hpo kinase activation occurs in phase separated "signalosomes" induced by clustering of upstream pathway components.

Synthesis of Block Copolymers Containing Stereoregular Pendant Electroactive Blocks.

The stereoregular nonconjugated pendant electroactive polymer (NCPEP) poly((N-carbazolylethylthio) propyl methacrylate) (PCzETPMA) has recently shown charge carrier mobilities that are on par with conjugated polymers. Here, we increased the complexity of the architecture for this NCPEP by introducing a polystyrene (PS) block via an anionic, living polymerization yielding a family of PS-b-PCzETPMA block copolymers as the first examples of NCPEP-block-copolymers with controlled stereoregularity of the NCPEP-blocks. Through this methodology we were able to control the molar masses, PS to PCzETPMA block ratios, and tacticities of the PCzETPMA-blocks. We found all three parameters to significantly impact the hole mobilities (µh) of the resulting copolymers, which increased with higher molar masses, longer PCzETPMA-blocks, and higher isotacticity of the PCzETPMA-block, giving the best µh of 2.33 × 10-5 cm2/V·s after annealing at 150 °C for the highest molar mass copolymer with a dominant isotactic PCzETPMA-block. This work is the first reported synthesis of a block copolymer bearing a NCPEP-block with a controlled tacticity and demonstrates that such complex polymer architectures can be realized with NCPEPs while maintaining control over their stereoregularity and without significantly suppressing the hole mobility in the resulting copolymers.

Recycling Heterogenous Catalysts for Multi-Batch Conjugated Polymer Synthesis via Direct Arylation Polymerization.

Despite the inherent sustainability direct arylation polymerization (DArP) offers through a C-H activation pathway, the use of expensive homogeneous Pd catalysts remains problematic for large-scale conjugated polymer (CP) synthesis. Herein, the first report on the recycling of heterogeneous catalysts for CP synthesis using DArP is presented. We found SiliaCat Pd-DPP to be a highly efficient and recyclable catalyst for multi-batch CP synthesis providing CPs with molecular weights (Mn) up to 82 kg/mol even after being recycled three times. Batch-to-batch variations were further optimized to afford up to five batches of polymers with a Mn of 25 ± 2.5 kg/mol without structural disparity. Significantly, this work discloses among the most sustainable CP synthesis protocols to date and presents the critical concept of catalyst-recycling to the important field of organic semiconducting polymers, which potentially enables access to truly low-cost flow chemistry for industrial-scale CP synthesis.

Par-3 family proteins in cell polarity & adhesion.

The Par-3/Baz family of polarity determinants is highly conserved across metazoans and includes C. elegans PAR-3, Drosophila Bazooka (Baz), human Par-3 (PARD3), and human Par-3-like (PARD3B). The C. elegans PAR-3 protein localises to the anterior pole of asymmetrically dividing zygotes with cell division cycle 42 (CDC42), atypical protein kinase C (aPKC), and PAR-6. The same C. elegans 'PAR complex' can also localise in an apical ring in epithelial cells. Drosophila Baz localises to the apical pole of asymmetrically dividing neuroblasts with Cdc42-aPKC-Par6, while in epithelial cells localises both in an apical ring with Cdc42-aPKC-Par6 and with E-cadherin at adherens junctions. These apical and junctional localisations have become separated in human PARD3, which is strictly apical in many epithelia, and human PARD3B, which is strictly junctional in many epithelia. We discuss the molecular basis for this fundamental difference in localisation, as well as the possible functions of Par-3/Baz family proteins as oligomeric clustering agents at the apical domain or at adherens junctions in epithelial stem cells. The evolution of Par-3 family proteins into distinct apical PARD3 and junctional PARD3B orthologs coincides with the emergence of stratified squamous epithelia in vertebrates, where PARD3B, but not PARD3, is strongly expressed in basal layer stem cells - which lack a typical apical domain. We speculate that PARD3B may contribute to clustering of E-cadherin, signalling from adherens junctions via Src family kinases or mitotic spindle orientation by adherens junctions in response to mechanical forces.

A picket fence function for adherens junctions in epithelial cell polarity.

Adherens junctions are a defining feature of all epithelial cells, providing cell-cell adhesion and contractile ring formation that is essential for cell and tissue morphology. In Drosophila, adherens junctions are concentrated between the apical and basolateral plasma membrane domains, defined by aPKC-Par6-Baz and Lgl/Dlg/Scrib, respectively. Whether adherens junctions contribute to apical-basal polarization itself has been unclear because neuroblasts exhibit apical-basal polarization of aPKC-Par6-Baz and Lgl in the absence of adherens junctions. Here we show that, upon disruption of adherens junctions in epithelial cells, apical polarity determinants such as aPKC can still segregate from basolateral Lgl, but lose their sharp boundaries and also overlap with Dlg and Scrib - similar to neuroblasts. In addition, control of apical versus basolateral domain size is lost, along with control of cell shape, in the absence of adherens junctions. Manipulating the levels of apical Par3/Baz or basolateral Lgl polarity determinants in experiments and in computer simulations confirms that adherens junctions provide a 'picket fence' diffusion barrier that restricts the spread of polarity determinants along the membrane to enable precise domain size control. Movement of adherens junctions in response to mechanical forces during morphogenetic change thus enables spontaneous adjustment of apical versus basolateral domain size as an emergent property of the polarising system.

Oncogenic BRAF, unrestrained by TGFß-receptor signalling, drives right-sided colonic tumorigenesis.

Right-sided (proximal) colorectal cancer (CRC) has a poor prognosis and a distinct mutational profile, characterized by oncogenic BRAF mutations and aberrations in mismatch repair and TGFß signalling. Here, we describe a mouse model of right-sided colon cancer driven by oncogenic BRAF and loss of epithelial TGFß-receptor signalling. The proximal colonic tumours that develop in this model exhibit a foetal-like progenitor phenotype (Ly6a/Sca1+) and, importantly, lack expression of Lgr5 and its associated intestinal stem cell signature. These features are recapitulated in human BRAF-mutant, right-sided CRCs and represent fundamental differences between left- and right-sided disease. Microbial-driven inflammation supports the initiation and progression of these tumours with foetal-like characteristics, consistent with their predilection for the microbe-rich right colon and their antibiotic sensitivity. While MAPK-pathway activating mutations drive this foetal-like signature via ERK-dependent activation of the transcriptional coactivator YAP, the same foetal-like transcriptional programs are also initiated by inflammation in a MAPK-independent manner. Importantly, in both contexts, epithelial TGFß-receptor signalling is instrumental in suppressing the tumorigenic potential of these foetal-like progenitor cells.

Wnt and Src signals converge on YAP-TEAD to drive intestinal regeneration.

Wnt signalling induces a gradient of stem/progenitor cell proliferation along the crypt-villus axis of the intestine, which becomes expanded during intestinal regeneration or tumour formation. The YAP transcriptional co-activator is known to be required for intestinal regeneration, but its mode of regulation remains controversial. Here we show that the YAP-TEAD transcription factor is a key downstream effector of Wnt signalling in the intestine. Loss of YAP activity by Yap/Taz conditional knockout results in sensitivity of crypt stem cells to apoptosis and reduced cell proliferation during regeneration. Gain of YAP activity by Lats1/2 conditional knockout is sufficient to drive a crypt hyperproliferation response. In particular, Wnt signalling acts transcriptionally to induce YAP and TEAD1/2/4 expression. YAP normally localises to the nucleus only in crypt base stem cells, but becomes nuclear in most intestinal epithelial cells during intestinal regeneration after irradiation, or during organoid growth, in a Src family kinase-dependent manner. YAP-driven crypt expansion during regeneration involves an elongation and flattening of the Wnt signalling gradient. Thus, Wnt and Src-YAP signals cooperate to drive intestinal regeneration.

Influence of Alkyl Chain Spacer Length on the Charge Carrier Mobility of Isotactic Poly(N-carbazolylalkyl acrylates).

In the search for semiconducting polymer alternatives to conjugated polymers, stereoregular nonconjugated pendant electroactive polymers (NCPEPs) have recently shown competitive hole mobilities with conjugated polymers and a dramatic increase in mobility relative to atactic analogues. Here we investigate one of the key structural variables of NCPEPs: the flexible alkyl spacer that separates the electroactive pendant from the backbone. We investigate a straightforward postpolymerization functionalization synthetic method to synthesize such polymers with high isotacticity using poly(N-carbazolylalkyl acrylate) as a model system, where the alkyl chain spacer in the NCPEPs is varied from 2 to 12 carbons. We observed that the hole mobility increased from the two-carbon spacer, resulting in the highest mobility upon thermal annealing with a four-carbon spacer for 75% isotactic polymers and with a six-carbon spacer for 87% isotactic polymers. As such, we have demonstrated an important role of the spacer chain in influencing mobility. For all spacer lengths, higher mobilities were measured with the more isotactic polymer. While physical characterization of the largely amorphous polymers yielded little insight into the structure-function relationships, DFT and MD simulations indicated helical structures for the polymers where intermolecular short-range π-stacking is observed and is affected by spacer chain length. This work demonstrates that both the degree of stereoregularity and the spacer chain length play a role in determining the hole mobility in NCPEPs.

p-Cymene: A Sustainable Solvent that is Highly Compatible with Direct Arylation Polymerization (DArP).

For over a decade, Direct Arylation Polymerization (DArP) has been demonstrated to be an eco-friendly, facile, and low-cost alternative to conventional methodologies such as Stille polymerization for conjugated polymer synthesis. By accessing through a C-H activation pathway, DArP offers a reduction of synthetic steps while eliminating the generation of stoichiometric, highly toxic organotin byproducts. However, as the major component in these reactions, the solvents most prevalently employed for DArP are hazardous and produced from unsustainable sources, such as dimethylacetamide (DMA), tetrahydrofuran (THF), and toluene. Although the use of sustainable alternative solvents such as 2-MeTHF and cyclopentyl methyl ether (CPME) has recently emerged, drawbacks of ethereal solvents include the need for a pressurized reaction setup as well as potential peroxide formation. While aromatic solvents are superior in solubilizing conjugated polymers, very little has been done in searching for more sustainable, benign alternatives for this class of solvent. Herein, we report the application of a sustainable, naturally sourced, high-boiling aromatic solvent, p-cymene, to DArP for the first time. p-Cymene was found to display excellent solubilizing ability in the synthesis of a broad scope of alternating copolymers with Mn up to 51.3 kg/mol and yields up to 96.2%, outperforming those prepared using CPME and toluene. Structural analysis revealed the exclusion of defects in these polymers prepared using p-cymene as the solvent which, in the case of a 2,2'-bithiophene monomer, is challenging to access through the use of conventional solvents for DArP, such as DMA and toluene.

Contrasting the Charge Carrier Mobility of Isotactic, Syndiotactic, and Atactic Poly((N-carbazolylethylthio)propyl methacrylate).

Isotactic nonconjugated pendant electroactive polymers (NCPEPs) have recently shown potential to achieve comparable charge carrier mobilities with conjugated polymers. Here we report the broader influence of tacticity in NCPEPs, using poly((N-carbazolylethylthio)propyl methacrylate) (PCzETPMA) as a model polymer. We utilized the thiol-ene reaction as an efficient postpolymerization functionalization method to achieve pendant polymers with high isotacticity and syndiotacticity. We found that a stereoregular isotactic polymer showed ∼100 times increased hole mobility (µh) as compared to both atactic and low molecular weight syndiotactic PCzETPMA, achieving µh of 2.19 × 10-4 cm2 V-1 s-1 after annealing at 120 °C. High molecular weight syndiotactic PCzETPMA gave ∼10 times higher µh than its atactic counterpart, comparable to isotactic PCzETPMA after annealing at 150 °C. Importantly, high molecular weight syndiotactic PCzETPMA showed a dramatic increase in µh to 1.82 × 10-3 cm2 V-1 s-1 when measured after annealing at 210 °C, which surpassed the well-known conjugated polymer poly(3-hexylthiophene) (P3HT) (µh = 4.51 × 10-4 cm2 V-1 s-1). MD simulations indicated short-range π-π stacked ordering in the case of stereoregular isotactic and syndiotactic polymers. This work is the first report of charge carrier mobilities in syndiotactic NCPEPs and demonstrates that the tacticity, annealing conditions, and molecular weight of NCPEPs can strongly affect µh.

From genes to shape during metamorphosis: a history.

Metamorphosis (Greek for a state of transcending-form or change-in-shape) refers to a dramatic transformation of an animal's body structure that occurs after development of the embryo or larva in many species. The development of a fly (or butterfly) from a crawling larva (or caterpillar) that forms a pupa (or chrysalis) before eclosing as a flying adult is a classic example of metamorphosis that captures the imagination and has been immortalized in children's books. Powerful genetic experiments in the fruit fly Drosophila melanogaster have revealed how genes can instruct the behaviour of individual cells to control patterns of tissue growth, mechanical force, cell-cell adhesion and cell-matrix adhesion drive morphogenetic change in epithelial tissues. Together, the distribution of mass, force and resistance determines cell shape changes, cell-cell rearrangements, and/or the orientation of cell divisions to generate the final form of the tissue. In organising tissue shape, genes harness the power of self-organisation to determine the collective behaviour of molecules and cells, which can often be reproduced in computer simulations of cell polarity and/or tissue mechanics. This review highlights fundamental discoveries in epithelial morphogenesis made by pioneers who were fascinated by metamorphosis, including D'Arcy Thompson, Conrad Waddington, Dianne Fristrom and Antonio Garcia-Bellido.

Author Correction: YAP1/TAZ drives ependymoma-like tumour formation in mice.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Control of skeletal morphogenesis by the Hippo-YAP/TAZ pathway.

The Hippo-YAP/TAZ pathway is an important regulator of tissue growth, but can also control cell fate or tissue morphogenesis. Here, we investigate the function of the Hippo pathway during the development of cartilage, which forms the majority of the skeleton. Previously, YAP was proposed to inhibit skeletal size by repressing chondrocyte proliferation and differentiation. We find that, in vitro, Yap/Taz double knockout impairs murine chondrocyte proliferation, whereas constitutively nuclear nls-YAP5SA accelerates proliferation, in line with the canonical role of this pathway in most tissues. However, in vivo, cartilage-specific knockout of Yap/Taz does not prevent chondrocyte proliferation, differentiation or skeletal growth, but rather results in various skeletal deformities including cleft palate. Cartilage-specific expression of nls-YAP5SA or knockout of Lats1/2 do not increase cartilage growth, but instead lead to catastrophic malformations resembling chondrodysplasia or achondrogenesis. Physiological YAP target genes in cartilage include Ctgf, Cyr61 and several matrix remodelling enzymes. Thus, YAP/TAZ activity controls chondrocyte proliferation in vitro, possibly reflecting a regenerative response, but is dispensable for chondrocyte proliferation in vivo, and instead functions to control cartilage morphogenesis via regulation of the extracellular matrix.

YAP1/TAZ drives ependymoma-like tumour formation in mice.

YAP1 gene fusions have been observed in a subset of paediatric ependymomas. Here we show that, ectopic expression of active nuclear YAP1 (nlsYAP5SA) in ventricular zone neural progenitor cells using conditionally-induced NEX/NeuroD6-Cre is sufficient to drive brain tumour formation in mice. Neuronal differentiation is inhibited in the hippocampus. Deletion of YAP1's negative regulators LATS1 and LATS2 kinases in NEX-Cre lineage in double conditional knockout mice also generates similar tumours, which are rescued by deletion of YAP1 and its paralog TAZ. YAP1/TAZ-induced mouse tumours display molecular and ultrastructural characteristics of human ependymoma. RNA sequencing and quantitative proteomics of mouse tumours demonstrate similarities to YAP1-fusion induced supratentorial ependymoma. Finally, we find that transcriptional cofactor HOPX is upregulated in mouse models and in human YAP1-fusion induced ependymoma, supporting their similarity. Our results show that uncontrolled YAP1/TAZ activity in neuronal precursor cells leads to ependymoma-like tumours in mice.