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Thanks to many promising properties, including biocompatibility and the ability to experience large deformations, poly(ethylene glycol) diacrylate (PEGDA) hydrogels are excellent candidate materials for a wide range of applications. Interestingly, the polymerization of PEGDA leads to a network microstructure that is fundamentally different from that of the "classic" polymeric gels. Specifically, PEGDA hydrogels comprise PEG chains that are interconnected by multifunctional densely grafted rod-like polyacrylates (PAs), which serve as cross-linkers. In this work, we derive a microstructurally motivated model that captures the essential features which enable deformation in PEGDA hydrogels: (1) entropic elasticity of PEG chains, (2) deformation of PA rods, and (3) PA-PA interactions. Expressions for the energy-density functions and the stress associated with each of the three contributions are derived. The model demonstrates the microstructural evolution of the network during loading and reveals the role of key microscopic quantities. To validate the model, we fabricate and compress PEGDA hydrogel discs. The model is in excellent agreement with our experimental findings for a broad range of PEGDA compositions. Interestingly, we show that the response of PEGDA hydrogels with short PEG chains and long PA rods is governed by PA-PA interactions, whereas networks with longer PEG chains are dominated by entropy. To enable design, we employ the model to investigate the influence of key microstructural quantities, such as the length of the PEG and the PA chains, on the macroscopic properties and response. The findings from this work pave the way to the efficient design of PEGDA hydrogels with tunable properties and behaviors, which will enable the optimization of their performance in various applications., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Performing conventional mechanical characterization techniques on soft materials can be challenging due to issues such as limited sample volumes and clamping difficulties. Deep indentation and puncture is a promising alternative as it is an information-rich measurement with the potential to be performed in a high-throughput manner. Despite its promise, the method lacks standardized protocols, and open questions remain about its possible limitations. Addressing these shortcomings is vital to ensure consistent methodology, measurements, and interpretation across samples and labs. To fill this gap, we examine the role of finite sample dimensions (and by extension, volume) on measured forces to determine the sample geometry needed to perform and unambiguously interpret puncture tests. Through measurements of puncture on a well-characterized elastomer using systematically varied sample dimensions, we show that the apparent mechanical response of a material is in fact sensitive to near-wall effects, and that additional properties, such as the sliding friction coefficient, can only be extracted in the larger dimension case where such effects are negligible.

We demonstrate that the sessile tunicate Botryllus schlosseri is remarkably resilient to applied loads by attaching the animals to an extensile substrate subjected to quasistatic equiradial loads. Animals can withstand radial extension of the substrate to strain values as high as 20% before they spontaneously detach. In the small to moderate strain regime, we found no relationship between the dynamic size of the external vascular bed and the magnitude of applied stretch, despite known force sensitivities of the vascular tissue at the cellular level. We attribute this resilience to the presence and mechanical properties of the tunic, the cellulose-enriched gel-like substance that encases the animal bodies and surrounding vasculature., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

The ability of cells to reorganize in response to external stimuli is important in areas ranging from morphogenesis to tissue engineering. While nematic order is common in biological tissues, it typically only extends to small regions of cells interacting via steric repulsion. On isotropic substrates, elongated cells can co-align due to steric effects, forming ordered but randomly oriented finite-size domains. However, we have discovered that flat substrates with nematic order can induce global nematic alignment of dense, spindle-like cells, thereby influencing cell organization and collective motion and driving alignment on the scale of the entire tissue. Remarkably, single cells are not sensitive to the substrate's anisotropy. Rather, the emergence of global nematic order is a collective phenomenon that requires both steric effects and molecular-scale anisotropy of the substrate. To quantify the rich set of behaviours afforded by this system, we analyse velocity, positional and orientational correlations for several thousand cells over days. The establishment of global order is facilitated by enhanced cell division along the substrate's nematic axis, and associated extensile stresses that restructure the cells' actomyosin networks. Our work provides a new understanding of the dynamics of cellular remodelling and organization among weakly interacting cells.

Bioinspired iron-catechol cross-links have shown remarkable success in increasing the mechanical properties of polymer networks, in part due to clustering of Fe 3+ -catechol domains which act as secondary network reinforcing sites. We report a versatile synthetic procedure to prepare modular PEG-acrylate networks with independently tunable covalent bis(acrylate) and supramolecular Fe 3+ -catechol cross-linking. Initial control of network structure is achieved through radical polymerization and cross-linking, followed by postpolymerization incorporation of catechol units via quantitative active ester chemistry and subsequent complexation with iron salts. By tuning the ratio of each building block, dual cross-linked networks reinforced by clustered iron-catechol domains are prepared and exhibit a wide range of properties (Young's moduli up to ∼245 MPa), well beyond the values achieved through purely covalent cross-linking. This stepwise approach to mixed covalent and metal-ligand cross-linked networks also permits local patterning of PEG-based films through masking techniques forming distinct hard, soft, and gradient regions., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Patient reviews provide an important referral source for physicians and an opportunity to improve practice performance. This study's objective was to characterize the online reviews of hip and knee arthroplasty surgeons published by three of the industry's leading platforms., Methods: A random sample of 1000 hip and knee arthroplasty surgeons across all 50 US states (10 hip and 10 knee surgeons per state) was generated using Google Search. A total of 7842 online reviews posted for those surgeons on Healthgrades, Vitals, and Google were analyzed. A range of surgeons, affiliated hospitals, and reviewer attributes was compared to identify significant predictors of patient satisfaction., Results: The study cohort had 98.1% male surgeons with a mean age of 53.55 ± 8.94 years and mean experience of 26.43 ± 9.21 years. Younger age (p < 0.001), shorter years of experience (p < 0.001), and arthroplasty fellowship training (p < 0.001) were associated with more positive ratings. Reviewer anonymity, observed in 30.93% of all reviews, tended to correlate with more negative ratings (p < 0.001). Overall, 86.93% of patient remarks were positive, and only 74.81% of remarks centered on physician attributes. The five leading components of patient satisfaction were perceptions of physician competence (34.81%, p < 0.001), bedside manner (23.83%, p = 0.002), and communication (16.17%, p = 0.94); interactions with physician extenders (14.75%, p < 0.001); and wait time (2.73%, p < 0.001)., Conclusion: While most ratings of hip and knee arthroplasty surgeons were positive, more than a quarter of reviews were either not directly related to the individual surgeons or were submitted anonymously. Caution is advised regarding overreliance on patient experience surveys as predictors of physician performance., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mohamad J. Halawi reports editorial/governing body memberships with The Journal of Bone and Joint Surgery, The Journal of Arthroplasty, and Arthroplasty Today. He also reports board membership/committee appointments with American Academy of Orthopaedic Surgeons and American Orthopaedic Association.

Surface-aligned liquid-crystal networks (LCNs) offer a solution for developing functional materials capable of performing a range of tasks, including actuation, shape memory, and surfaces patterning. Here we show that Diels-Alder cycloaddition can be used to prepare the backbone of planar aligned LCNs under mild ambient conditions without the addition of additives or UV irradiation. The mechanical properties of the networks have robust viscoelastic modulus and stiffness with a reversible local free volume change upon physical aging. This study shows new opportunities to design surface-aligned LCNs based on additive free step-growth Diels-Alder polymerization and enables the potential to incorporate a wider range of photochromic materials into LCNs.

Here we present a new, compact magnetic tweezers design that enables precise application of a wide range of dynamic forces to soft materials without the need to raise or lower the magnet height above the sample. This is achieved through the controlled rotation of the permanent magnet array with respect to the fixed symmetry axis defined by a custom-built iron yoke. These design improvements increase the portability of the device and can be implemented within existing microscope setups without the need for extensive modification of the sample holders or light path. This device is particularly well-suited to active microrheology measurements using either creep analysis, in which a step force is applied to a micron-sized magnetic particle that is embedded in a complex fluid, or oscillatory microrheology, in which the particle is driven with a periodic waveform of controlled amplitude and frequency. In both cases, the motions of the particle are measured and analyzed to determine the local dynamic mechanical properties of the material.

Anaerobic gut fungi (AGF) are lignocellulose degraders that naturally form biofilms in the rumen of large herbivores and in standard culture techniques. While biofilm formation enhances biomass degradation and carbohydrate-active enzyme (CAZyme) production in some bacteria and aerobic fungi, gene expression and metabolism in AGF biofilms have not been compared to non-biofilm cultures. Here, using the tunable morphology of the non-rhizoidal AGF, Caecomyces churrovis, the impacts of biofilm formation on AGF gene expression, metabolic flux, growth rate, and xylan degradation rate are quantified to inform future industrial scale-up efforts. Contrary to previous findings, C. churrovis upregulated catabolic CAZymes in stirred culture relative to biofilm culture. Using a de novo transcriptome, 197 new transcripts with predicted CAZyme function were identified. Stirred cultures grew and degraded xylan significantly faster than biofilm-forming cultures with negligible differences in primary metabolic flux, offering a way to accelerate AGF biomass valorization without altering the fermentation product profile. The rhizoidal AGF, Neocallimastix lanati, also grew faster with stirring on a solid plant substrate, suggesting that the advantages of stirred C. churrovis cultures may apply broadly to other AGF., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Materials that utilize heterogeneous microstructures to control macroscopic mechanical response are ubiquitous in nature. Yet, translating nature's lessons to create synthetic soft solids has remained challenging. This is largely due to the limited synthetic routes available for creating soft composites, particularly with submicron features, as well as uncertainty surrounding the role of such a microstructured secondary phase in determining material behavior. This work leverages recent advances in the development of photocrosslinkable thermogelling nanoemulsions to produce composite hydrogels with a secondary phase assembled at well controlled length scales ranging from tens of nm to tens of μm. Through analysis of the mechanical response of these fluid-filled composite hydrogels, it is found that the size scale of the secondary phase has a profound impact on the strength when at or above the elastofracture length. Moreover, this work shows that mechanical integrity of fluid-filled soft solids can be sensitive to the size scale of the secondary phase.

An important but often overlooked feature of Diels-Alder (DA) cycloadditions is the ability for DA adducts to undergo mechanically induced cycloreversion when placed under force. Herein, we demonstrate that the commonly employed DA cycloaddition between furan and maleimide to crosslink hydrogels results in slow gelation kinetics and "mechanolabile" crosslinks that relate to reduced material strength. Through rational computational design, "mechanoresistant" DA adducts were identified by constrained geometries simulate external force models and employed to enhance failure strength of crosslinked hydrogels. Additionally, utilization of a cyclopentadiene derivative, spiro[2.4]hepta-4,6-diene, provided mechanoresistant DA adducts and rapid gelation in minutes at room temperature. This study illustrates that strategic molecular-level design of DA crosslinks can provide biocompatible materials with improved processing, mechanical durability, lifetime, and utility.

Evolution of composition, rheology, and morphology during phase separation in complex fluids is highly coupled to rheological and mass transport processes within the emerging phases, and understanding this coupling is critical for materials design of multiphase complex fluids. Characterizing these dependencies typically requires careful measurement of a large number of equilibrium and transport properties that are difficult to measure in situ as phase separation proceeds. Here, we propose and demonstrate a high-throughput microscopy platform to achieve simultaneous, in situ mapping of time-evolving morphology and microrheology in phase separating complex fluids over a large compositional space. The method was applied to a canonical example of polyelectrolyte complex coacervation, whereby mixing of oppositely charged species leads to liquid-liquid phase separation into distinct solute-dense and dilute phases. Morphology and rheology were measured simultaneously and kinetically after mixing to track the progression of phase separation. Once equilibrated, the dense phase viscosity was determined to high compositional accuracy using passive probe microrheology, and the results were used to derive empirical relationships between the composition and viscosity. These relationships were inverted to reconstruct the dense phase boundary itself, and further extended to other mixture compositions. The resulting predictions were validated by independent equilibrium compositional measurements. This platform paves the way for rapid screening and formulation of complex fluids and (bio)macromolecular materials, and serves as a critical link between formulation and rheology for multi-phase material discovery.

Recent far-reaching advances in synthetic biology have yielded exciting tools for the creation of new materials. Conversely, advances in the fundamental understanding of soft-condensed matter, polymers and biomaterials offer new avenues to extend the reach of synthetic biology. The broad and exciting range of possible applications have substantial implications to address grand challenges in health, biotechnology and sustainability. Despite the potentially transformative impact that lies at the interface of synthetic biology and biomaterials, the two fields have, so far, progressed mostly separately. This Perspective provides a review of recent key advances in these two fields, and a roadmap for collaboration at the interface between the two communities. We highlight the near-term applications of this interface to the development of hierarchically structured biomaterials, from bioinspired building blocks to 'living' materials that sense and respond based on the reciprocal interactions between materials and embedded cells., (© 2022. Springer Nature Limited.)

Marine mussels have the remarkable ability to adhere to a variety of natural and artificial surfaces under hostile environmental conditions. Although the molecular composition of mussel adhesives has been well studied, a mechanistic understanding of the physical origins of mussels' impressive adhesive strength remains elusive. Here, we investigated the role of substrate geometry in the adhesive performance of mussels. Experimentally, we created substrates with differing surface properties using 3D printing and laser drilling and introduced these to mussels, which in turn adhered to the engineered surfaces via plaque-thread byssal structures. Tensile testing with in situ imaging was conducted to quantify the adhesion strength of the mussel plaques, and the microstructures of the mechanically deformed plaques were characterized using scanning electron microscopy. Our results reveal that the geometry of the surfaces has no significant impact on the detachment force and the strain, whereas the change in adhesion area leads to a different adhesion stress. Ultrastructural analysis confirms the expected presence of an open-cell foamy network coated with the cuticle. The observed detachment dynamics and failure mechanisms do vary depending on the substrate properties, suggesting the presence of substrate-dependent nonuniform stress distributions at the interface. Together, these results show mussels' remarkable ability to adapt to differing physical conditions and demonstrate the importance of the on-demand and in situ manufacturing of the stiff cuticle and relatively compliant adhesive interlayer. The resultant composite structure avoids the formation of prestress during the formation of the adhesive joint, provides conformability to the surface, and helps compensate for local bending interactions to maintain adhesive strength. Our findings suggest forward design strategies to improve adhesive performance on complex surfaces.

The porous core of the marine mussel provides mechanical advantages of achieving substantial deformation and high toughness. Inspired by the unique mechanical behaviours of mussel plaque cores, the present study develops ultra-soft, stretchable and tough cellular solids by bio-mimicking their porosity and properties. Although scaling laws to correlate the mechanical properties of cellular solids with bulk materials have been established, they are primarily based on experimental data from stiff cellular solids. In this article, the scaling law for soft cellular solids is studied to relate tensile properties and toughness with volume fractions. Unlike conventional stiff cellular solids, the scaling law shows that soft lattices experience bending-dominated deformation at the elastic state and fail under stretching-dominated deformation. Uniaxial and planar tensile tests demonstrate that the proposed soft lattices achieved Young's modulus of 0.04∼0.17 MPa, failure strain of 135.5∼213.9% and toughness of 582∼941 J m−2 by manipulating the volume fraction (0.2∼0.5), positioning them as softer, more stretchable and tougher than the majority of engineering foams in the Ashby diagram. In addition, the toughness of soft lattices is found to be sensitive to volume fraction but insensitive to initial crack length, thickness and height (≥20mm). Two distinct failure modes, truss failure and joint failure, are correlated with volume fraction. The soft lattice with a volume fraction (around 0.4) similar to mussel plaque fails at the transition of these two failure modes and achieves the highest toughness. This study contributes new insights to the materials science community and lays the foundation for the development of lightweight, damage-tolerant and high-performance metamaterials. [ABSTRACT FROM AUTHOR]

Macrophages play a pivotal role in the healing of diabetic ulcers. The sustained elevation of glucose levels damages the insulin signaling pathway in macrophages, leading to dysfunctional macrophages that struggle to transition from pro-inflammatory (M1) to reparative (M2) states. Therefore, modulating macrophage inflammatory responses via the insulin pathway holds promise for diabetic ulcer treatment. Additionally, the presence of biofilm impedes drug penetration, and the resulting immunosuppressive microenvironment exacerbates the persistent infiltration of pro-inflammatory M1 macrophages. Therefore, we designed an array of dissolvable microneedle (denoted as NPF@MN) loaded with self-assembled nanoparticles that could deliver NPF nanoparticles, acid-sensitive NPF-releasing Protocatechualdehyde (PA) with hypoglycemic and insulin-like effects, regulating macrophage polarization to an anti-inflammatory M2 phenotype. Additionally, this study extensively examined the mechanism by which NPF@MN accelerates the healing of diabetic ulcers through the activation of the insulin signaling pathway. Through RNA-seq and GSEA analysis, we identified a reduction in the expression of pathway-related factors such as IR, IRS-1, IRS-2, and SHC. Our work presents an innovative therapeutic approach targeting the insulin pathway in diabetic ulcers and underscores its translational potential for clinical management. [ABSTRACT FROM AUTHOR]

Quantifying the response of marine mussel plaque attachment to wet surfaces remains a significant challenge to a mechanistic understanding of plaque adhesion. Here, we develop a novel, customized microscope system, combined with two-dimensional in situ digital image correlation (DIC), to quantify the in-plane deformation of a deformable substrate that interacts with a mussel plaque under directional tension. By examining the strain field within the substrate, we acquired an understanding of the mechanism by which in-plane traction forces are transmitted from the mussel plaque to the underlying substrate. Finite-element (FE) models were developed to assist in the interpretation of the experimental measurement. Our study revealed a synergistic effect of pulling angle and substrate stiffness on plaque detachment, with mussel plaques anchoring to a 'stiff' substrate at small pulling angles, i.e. natural anchoring angles, having mechanical advantages with higher load-bearing capacity and less plaque deformation. We identify two distinct failure modes, i.e. shear-traction-governed failure (STGF) and normal-traction-governed failure (NTGF). It was found that increasing the stiffness of the substrate or reducing the pulling angle results in a change of the failure mode from NTGF to STGF. Our findings offer new insights into the mechanistic understanding of mussel plaque–substrate interaction, providing a plaque-inspired strategy to develop high-performance and artificial wet adhesion. [ABSTRACT FROM AUTHOR]

IgA nephropathy (IgAN) is characterized by glomerular deposition of immune complexes (ICs) consisting of IgA1 with O-glycans deficient in galactose (Gd-IgA1) and Gd-IgA1-specific IgG autoantibodies. These ICs induce kidney injury, and in the absence of diseasespecific therapy, up to 40% of patients with IgAN progress to kidney failure. IgA1 with its clustered O-glycans is unique to humans, which hampered development of small-animal models of IgAN. Here, we used a model wherein engineered ICs (EICs) formed from human Gd-IgA1 and recombinant human IgG autoantibody are injected into nude mice to induce glomerular injury mimicking human IgAN. In this model, we assessed the protective effects of sparsentan, a single-molecule dual endothelin angiotensin receptor antagonist (DEARA) versus vehicle on EIC-induced glomerular proliferation and dysregulation of gene expression in the kidney. Oral administration of sparsentan (60 or 120 mg/kg daily) to mice intravenously injected with EIC attenuated the EIC-induced glomerular hypercellularity. Furthermore, analysis of changes in the whole kidney transcriptome revealed that key inflammatory and proliferative biological genes and pathways that are upregulated in this EIC model of IgAN were markedly reduced by sparsentan, including complement genes, integrin components, members of the mitogen-activated protein kinase family, and Fc receptor elements. Partial overlap between mouse and human differentially expressed genes in IgAN further supported the translational aspect of the immune and inflammatory components from our transcriptional findings. In conclusion, our data indicate that in the mouse model of IgAN, sparsentan targets immune and inflammatory processes leading to protection from mesangial hypercellularity. [ABSTRACT FROM AUTHOR]

The unstable behavior of the isotropic, compressible Mooney-Rivlin hyperelastic model is investigated and described. The constitutive equation is parameterized with the help of the ground-state Poisson's ratio and the dimensionless ratio of the material parameters C 01 and C 10 . Transverse stretch solutions are obtained for standard homogeneous loading modes, and the stress solutions are computed numerically for the physically permitted range of the ground-state Poisson's ratio. We introduce a numerical technique to isolate subdomains with non-unique transverse stretch responses. Our analysis revealed some limitations of the model and allowed us to make critical observations about the strengths and weaknesses of the model. The analyses we present are essential to understand the characteristics of this widely used hyperelastic model. The novel results have important implications for the application of the isotropic, compressible Mooney-Rivlin hyperelastic material model. [ABSTRACT FROM AUTHOR]

Modulating reversible isomerization of hydrophobic dyes in aqueous solutions is greatly desired. Here we report on reversible isomerization of solvatochromic donor-acceptor Stenhouse adducts (DASAs) in water through the confinement from dendritic oligoethylene glycols (OEGs). Dendronization of DASAs with dendritic OEGs affords them characteristic thermoresponsiveness. These dendronized DASAs spontaneously isomerize in water from hydrophobic linear state into hydrophilic cyclic state at room temperature due to the strong hydration. However, hydrophobic microenvironment through thermally dehydration and collapse of the dendritic OEGs at elevated temperatures confines hydration of the DASA moieties and mediates their interactions with the collapsed hydrophobic OEG domains, affording their isomerization recovery in water efficiently from the hydrophilic cyclic state into the hydrophobic linear state. The confinement-mediated reversible isomerization of DASA moieties in water can be repeated through alternative photo-irradiation and thermal dehydrations, exhibiting excellent fatigue resistance. [ABSTRACT FROM AUTHOR]

In this paper, we have analyzed behavior of the generalized compressible isotropic Blatz–Ko model and the so-called basic-Hencky model in the framework of a coupled axial-stretching to simple shear test under the plane stress condition. The mechanical behavior depends on both the stretching-direction, i.e. Θ and magnitude of displacement, i.e. γ prescribed on the sample edge. Based on, we have computed the transverse stretch versus longitudinal stretch. We have shown that, the approximate displacement field cannot be sustained in the context of BK-model. In contrast, results of FE-simulations show that, this deformation field can be maintained for appropriate value of Poisson's ratio and porosity parameter. Also, the Poisson's function was revisited in the context of BK-model and basic-Hencky model; a difference was highlighted. Besides, it turns out advantageous to use compressible isotropic logarithmic-strain-energy to model behavior of compressible isotropic rubber-like materials in the range of moderate strains. Some Finite Element simulations have been performed in order to validate our findings. [ABSTRACT FROM AUTHOR]

Digital light processing (DLP) 3DP, commercial acrylate-based photocurable resins, and thermally expandable microspheres-incorporated flexible photocurable resins were employed to fabricate an SPE column with a thermally expanded monolithic foam for extracting Mn, Co, Ni, Cu, Zn, Cd, and Pb ions prior to the determination using inductively coupled plasma mass spectrometry. After optimization of the thermally activated foaming, the design and fabrication of the SPE column, and the automatic analytical system, the DLP 3D-printed SPE column with the thermally expanded monolithic foam extracted the metal ions with up to 14.8-fold enhancement (relative to that without incorporating the microspheres), with absolute extraction efficiencies all higher than 95.6%, and method detection limits in the range from 0.5 to 5.2 ng L -1 . We validated the reliability and applicability of this method by determination of the metal ions in several reference materials (CASS-4, SLRS-5, 1643f, and Seronorm Trace Elements Urine L-2) and spiked seawater, river water, ground water, and human urine samples. The results illustrated that to incorporate the thermally expandable microspheres into the photocurable resins with a post-printing heating treatment enabled the DLP 3D-printed thermally expanded monolithic foam to substantially improve the extraction of the metal ions, thereby extending the applicability of SPE devices fabricated by vat photopolymerization 3DP techniques., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The implications of the existence of different actins expressed in epithelial cells for network mechanics and dynamics is investigated by microrheology and confocal imaging. γ-actin predominately found in the apical cortex forms stiffer networks compared to β-actin, which is preferentially organized in stress fibers. We attribute this to selective interactions with Mg2+-ions interconnecting the filaments' N-termini. Bundling propensity of the isoforms is different in the presence of Mg2+-ions, while crosslinkers such as α-actinin, fascin, and heavy meromyosin alter the mechanical response independent of the isoform. In the presence of myosin, β-actin networks show a large number of small contraction foci, while γ-actin displays larger but fewer foci indicative of a stronger interaction with myosin motors. We infer that subtle changes in the amino acid sequence of actin isoforms lead to alterations of the mechanical properties on the network level with potential implications for specific biological functions. β-actin and γ-actin are nearly identical, and yet incorporate into different cytoskeletal structures. Here, the authors create isoform-pure reconstituted networks and study their structural and mechanical differences, underscoring the significance of the isoforms in diverse cellular functions. [ABSTRACT FROM AUTHOR]

Aneuploidy seriously compromises female fertility and increases incidence of birth defects. Rates of aneuploidy in human eggs from even young women are significantly higher than those in other mammals. However, intrinsic genetic factors underlying this high incidence of aneuploidy in human eggs remain largely unknown. Here, we found that ectopic expression of human TUBB8 in mouse oocytes increases rates of aneuploidy by causing kinetochore–microtubule (K–MT) attachment defects. Stretched bivalents in mouse oocytes expressing TUBB8 are under less tension, resulting in continuous phosphorylation status of HEC1 by AURKB/C at late metaphase I that impairs the established correct K–MT attachments. This reduced tension in stretched bivalents likely correlates with decreased recruitment of KIF11 on meiotic spindles. We also found that ectopic expression of TUBB8 without its C-terminal tail decreases aneuploidy rates by reducing erroneous K–MT attachments. Importantly, variants in the C-terminal tail of TUBB8 were identified in patients with recurrent miscarriages. Ectopic expression of an identified TUBB8 variant in mouse oocytes also compromises K–MT attachments and increases aneuploidy rates. In conclusion, our study provides novel understanding for physiological mechanisms of aneuploidy in human eggs as well as for pathophysiological mechanisms involved in recurrent miscarriages. [ABSTRACT FROM AUTHOR]

Background: The discovery of lead compounds is fundamental to herbicide innovation, yet the limited availability of valuable lead compounds has impeded their progress in recent years. The study presents a novel molecular scaffold that exhibits remarkably potent herbicidal activity., Results: Through a scaffold-hopping strategy, a highly potent lead compound for herbicides, namely 3-(2-pyridinyl)-benzothiazol-2-one, was unexpectedly discovered during attempts to structurally modify haloxyfop, a commercial aryl-oxy-phenoxy-propionate herbicide. To investigate the structure-activity relationship (SAR) of the newly discovered herbicidal chemicals, a series of 2-(2-oxo-3-(pyridin-2-yl)-2,3-dihydrobenzo[d]thiazol-6-yloxy)propanoic acid derivatives, I-01 ~ I-27, were designed and synthesized. SAR analysis revealed that trifluoromethyl at the 5-position of pyridine is crucial for herbicidal activity, whereas additional fluorine or Cl atom at the 3-position of pyridine significantly enhances activity. Carboxylic ester derivatives exhibit superior herbicidal activity compared with amide derivatives. Moreover, the activity of carboxylic ester derivatives decreases with C chain extension, but the introduction of O atoms in the side chain benefits activity enhancement. Pot experiments conducted in a glasshouse demonstrated that I-01 and I-09 exhibited potent postemergence herbicidal activity against broadleaf weeds, and completely inhibited growth of Amaranthus retroflex, Abutilon theophrasti and Portulaca oleracea at a dosage of 75 g ha -1 ., Conclusion: Despite the initial goal of scaffold-hopping not being achieved, we have successfully identified a novel molecular scaffold exhibiting exceptional herbicidal activity, thereby presenting innovative prospects for herbicide development. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Magnetic tweezers have emerged as a vital force spectroscopy tool for characterizing the mechanical properties of nucleic acids and their interactions with proteins. Harnessing the principles of magnetic theory, magnetic tweezers allow for the precise manipulation of biological compounds at the single-molecule level through the imposition of a magnetic field. This review focuses on the application of magnetic tweezers in the context of DNA studies, with a particular emphasis on the mechanical properties of DNA and its dynamic interactions with proteins and enzymes. These interactions are essential to genomic transactions such as DNA replication, repair, and transcription. Over the last few decades, magnetic tweezer technology has experienced significant advancements, leading to the development of different types of magnetic tweezers. These technological breakthroughs have opened up new avenues of scientific research, including studies related to DNA elasticity, supercoiling, replication, and repair. [ABSTRACT FROM AUTHOR]

Soft materials that can demonstrate on demand reconfigurability and changing compliance are highly sought after as actuator materials in many fields such as soft robotics and biotechnology. Whilst there are numerous proof of concept materials and devices, rigorous predictive models of deformation have not been well-established or widely adopted. In this paper, we discuss programming complex three-dimensional deformations of a soft intrinsically anisotropic material by controlling the orientation of the contractile units and/or direction of the applied electric field. Programming is achieved by patterning contractile units and/or selectively activating spatial regions. A new constitutive model is derived to describe the soft intrinsic anisotropy of soft materials. The model is developed within a continuum mechanics framework using an invariant-based formulation. Computational implementation allows us to simulate the complex three-dimensional shape response when activated by electric field. Several examples of the achievable Gauss-curved surfaces are demonstrated. Our computational analysis introduces a mechanics-based framework for design when considering soft morphing materials with intrinsic anisotropy, and is meant to inspire the development of new soft active materials. [ABSTRACT FROM AUTHOR]

Aqueous two-phase systems (ATPS) provide imperative interfaces and compartments in biology, but the sculpture and conversion of liquid structures to functional solids is challenging. Here, inspired by phase evolution of mussel foot proteins ATPS, we tackle this problem by designing poly(ionic liquids) capable of responsive condensation and phase-dependent curing. When mixed with poly(dimethyl diallyl ammonium chloride), the poly(ionic liquids) formed liquid condensates and ATPS, which were tuned into bicontinuous liquid phases under stirring. Selective, rapid curing of the poly(ionic liquids)-rich phase was facilitated under basic conditions (pH 11), leading to the liquid-to-gel conversion and structure sculpture, i.e., the evolution from ATPS to macroporous sponges featuring bead-and-string networks. This mechanism enabled the selective embedment of carbon nanotubes in the poly(ionic liquids)-rich phase, which showed exceptional stability in harsh conditions (10 wt% NaCl, 80 oC, 3 days) and high (2.5 kg/m2h) solar thermal desalination of concentrated salty water under 1-sun irradiation. Aqueous two-phase systems form interfaces and compartments, but converting the liquid structures to functional solids is challenging. Here, the authors use poly(ionic liquids) to form such systems, which can then be converted to gels and used for desalination. [ABSTRACT FROM AUTHOR]

Vascular endothelial protein tyrosine phosphatase (VE‐PTP) influences endothelial barrier function by regulating the activation of tyrosine kinase receptor Tie2. We determined whether this action is linked to the development of atherosclerosis by examining the influence of arterial shear stress on VE‐PTP, Tie2 activation, plasma leakage, and atherogenesis. We found that exposure to high average shear stress led to downstream polarization and endocytosis of VE‐PTP accompanied by Tie2 activation at cell junctions. In aortic regions with disturbed flow, VE‐PTP was not redistributed away from Tie2. Endothelial cells exposed to high shear stress had greater Tie2 activation and less macromolecular permeability than regions with disturbed flow. Deleting endothelial VE‐PTP in VE‐PTPiECKO mice increased Tie2 activation and reduced plasma leakage in atheroprone regions. ApoE−/− mice bred with VE‐PTPiECKO mice had less plasma leakage and fewer atheromas on a high‐fat diet. Pharmacologic inhibition of VE‐PTP by AKB‐9785 had similar anti‐atherogenic effects. Together, the findings identify VE‐PTP as a novel target for suppression of atherosclerosis. Synopsis: Laminar shear stress reduces plasma leakage and atheroma formation in atheroprotected regions of the aorta through downstream polarization and endocytosis of VE‐PTP and resultant activation of Tie2. Atherosclerosis can be suppressed by inhibition of VE‐PTP in atheroprone regions that lack VE‐PTP sequestration. The membrane tyrosine phosphatase VE‐PTP is redistributed to the downstream pole of endothelial cells in regions of the aorta with laminar flow but not in regions with turbulent flow.Downstream polarization of VE‐PTP is followed by endocytosis, leading to VE‐PTP sequestration, activation of Tie2 at endothelial junctions, increased junctional integrity, and reduced leakage.Lack of VE‐PTP redistribution and sequestration in atheroprone regions results in less Tie2 activity and greater leakage and atheroma formation in ApoE−/− mice but can be reversed by administering a VE‐PTP inhibitor.The suppressive effect of the VE‐PTP inhibitor on atherosclerosis development can be mimicked by inactivating VE‐PTP gene expression in endothelial cells of ApoE−/−/VE‐PTPiECKO mice. [ABSTRACT FROM AUTHOR]

Despite their role in host nutrition, the anaerobic gut fungal (AGF) component of the herbivorous gut microbiome remains poorly characterized. Here, to examine global patterns and determinants of AGF diversity, we generate and analyze an amplicon dataset from 661 fecal samples from 34 mammalian species, 9 families, and 6 continents. We identify 56 novel genera, greatly expanding AGF diversity beyond current estimates (31 genera and candidate genera). Community structure analysis indicates that host phylogenetic affiliation, not domestication status and biogeography, shapes the community rather than. Fungal-host associations are stronger and more specific in hindgut fermenters than in foregut fermenters. Transcriptomics-enabled phylogenomic and molecular clock analyses of 52 strains from 14 genera indicate that most genera with preferences for hindgut hosts evolved earlier (44-58 Mya) than those with preferences for foregut hosts (22-32 Mya). Our results greatly expand the documented scope of AGF diversity and provide an ecologically and evolutionary-grounded model to explain the observed patterns of AGF diversity in extant animal hosts. Anaerobic gut fungi are a functionally important component of mammalian herbivores' microbiomes. Here, the authors surveys anaerobic gut fungi in 34 species of ruminants and hindgut fermenters, assessing their patterns and identifying 56 novel genera. [ABSTRACT FROM AUTHOR]

Kinesins constitute a superfamily of microtubule (MT)-based motor proteins, which can perform diverse biological functions in cells such as transporting vesicle, regulating MT dynamics, and segregating chromosome. Some motors such as kinesin-1, kinesin-2, and kinesin-3 do the activity mainly on the MT lattice, while others such as kinesin-7 and kinesin-8 do the activity mainly at the MT plus end. To perform the different functions, it is required that the former motors can reside on the MT lattice for longer times than at the end, while the latter motors can reside at the MT plus end for long times. Here, a simple but general theory of the MT-end residence time of the kinesin motor is presented, with which the factors dictating the residence time are determined. The theory is further used to study specifically the MT-end residence times of Drosophila kinesin-1, kinesin-2/KIF3AB, kinesin-3/Unc104, kinesin-5/Eg5, kinesin-7/CENP-E, and kinesin-8/Kip3 motors, with the theoretical results being in agreement with the available experimental data. [ABSTRACT FROM AUTHOR]

The most widely-used representation of the compressible, isotropic, neo-Hookean hyperelastic model is considered in this paper. The version under investigation is that which is implemented in the commercial finite element software ABAQUS, ANSYS and COMSOL. Transverse stretch solutions are obtained for the following homogeneous deformations: uniaxial loading, equibiaxial loading in plane stress, and uniaxial loading in plane strain. The ground-state Poisson's ratio is used to parameterize the constitutive model, and stress solutions are computed numerically for the physically permitted range of its values. Despite its broad application to a number of engineering problems, the physical limitations of the model, particularly in the small to moderate stretch regimes, are not explored. In this work, we describe and analyze results and make some critical observations, underlining the model's advantages and limitations. For example, a snap-back feature of the transverse stretch is identified in uniaxial compression, a physically undesirable behavior unless validated by experimental data. The domain of this non-unique solution is determined in terms of the ground-state Poisson's ratio and the state of stretch and stress. The analyses we perform are essential to enable the understanding of the characteristics of the standard, compressible, isotropic, neo-Hookean model used in ABAQUS, ANSYS and COMSOL. In addition, our results provide a framework for the parameter-fitting procedure needed to characterize this standard, compressible, isotropic neo-Hookean model in terms of experimental data. [ABSTRACT FROM AUTHOR]

Two-point microrheology was applied to a homogeneous (DPPC monolayers) and a heterogeneous (asphaltene films) interface. For DPPC monolayers, both the longitudinal and transverse-correlated motions showed a purely diffusional regime at different surface pressures. A good agreement between the single particle and two particle mean square displacements was observed. For asphaltene films, a transition from viscous to viscoelastic regime was observed as the interface aged. The thermal cross-correlations of particles showed a strong scattering over the particle distances evidence of the heterogeneity of the asphaltene films. This heterogeneity was also reflected in the mean square displacements where discrepancies are observed between results from one particle and two particle microrheology. Choosing one single particle as reference, a map of the spatial heterogeneity of asphaltene films was developed. The novel methodology provides insights into local micromechanics of complex interfaces that is not accessible with classical interfacial rheometry. [ABSTRACT FROM AUTHOR]

Introduction: Myosin II has been investigated with optical trapping, but single motor-filament assay arrangements are not reflective of the complex cellular environment. To understand how myosin interactions propagate up in scale to accomplish system force generation, we devised a novel actomyosin ensemble optical trapping assay that reflects the hierarchy and compliancy of a physiological environment and is modular for interrogating force effectors. Methods: Hierarchical actomyosin bundles were formed in vitro. Fluorescent template and cargo actin filaments (AF) were assembled in a flow cell and bundled by myosin. Beads were added in the presence of ATP to bind the cargo AF and activate myosin force generation to be measured by optical tweezers. Results: Three force profiles resulted across a range of myosin concentrations: high force with a ramp-plateau, moderate force with sawtooth movement, and baseline. The three force profiles, as well as high force output, were recovered even at low solution concentration, suggesting that myosins self-optimize within AFs. Individual myosin steps were detected in the ensemble traces, indicating motors are taking one step at a time while others remain engaged in order to sustain productive force generation. Conclusions: Motor communication and system compliancy are significant contributors to force output. Environmental conditions, motors taking individual steps to sustain force, the ability to backslip, and non-linear concentration dependence of force indicate that the actomyosin system contains a force-feedback mechanism that senses the local cytoskeletal environment and communicates to the individual motors whether to be in a high or low duty ratio mode. [ABSTRACT FROM AUTHOR]

The cytoplasm is highly organized. However, the extent to which this organization influences the dynamics of cytoplasmic proteins is not well understood. Here, we use Xenopus laevis egg extracts as a model system to study diffusion dynamics in organized versus disorganized cytoplasm. Such extracts are initially homogenized and disorganized, and self-organize into cell-like units over the course of tens of minutes. Using fluorescence correlation spectroscopy, we observe that as the cytoplasm organizes, protein diffusion speeds up by about a factor of two over a length scale of a few hundred nanometers, eventually approaching the diffusion time measured in organelle-depleted cytosol. Even though the ordered cytoplasm contained organelles and cytoskeletal elements that might interfere with diffusion, the convergence of protein diffusion in the cytoplasm toward that in organelle-depleted cytosol suggests that subcellular organization maximizes protein diffusivity. The effect of organization on diffusion varies with molecular size, with the effects being largest for protein-sized molecules, and with the time scale of the measurement. These results show that cytoplasmic organization promotes the efficient diffusion of protein molecules in a densely packed environment. Cytoplasmic organization is a hallmark of living cells. Here, the authors make use of self-organizing cell extracts to examine how the emergence of large-scale organizations influences the microscopic diffusion of protein molecules in the cytoplasm. [ABSTRACT FROM AUTHOR]

Background: Skin tissue is vital in protecting the body from injuries and bacterial infections. Wound infection caused by bacterial colonization is one of the main factors hindering wound healing. Wound infection caused by colonization of a large number of bacteria can cause the wound to enter a continuous stage of inflammation, which delays wound healing. Hydrogel wound dressing is composed of natural and synthetic polymers, which can absorb tissue fluid, improve the local microenvironment of wound, and promote wound healing. However, in the preparation process of hydrogel, the complex preparation process and poor biological efficacy limit the application of hydrogel wound dressing in complex wound environment. Therefore, it is particularly important to develop and prepare hydrogel dressings with simple technology, good physical properties and biological effects by using natural polymers. Results: In this study, a gelatin-based (Tsg-THA&Fe) hydrogel was created by mixing trivalent iron (Fe3+) and 2,3,4-trihydroxybenzaldehyde (THA) to form a complex (THA&Fe), followed by a simple Schiff base reaction with tilapia skin gelatin (Tsg). The gel time and rheological properties of the hydrogels were adjusted by controlling the number of complexes. The dynamic cross-linking of the coordination bonds (o-phthalmictriol-Fe3+) and Schiff base bonds allows hydrogels to have good self-healing and injectable properties. In vitro experiments confirmed that the hydrogel had good biocompatibility and biodegradability as well as adhesion, hemostasis, and antibacterial properties. The feasibility of Tsg-THA&Fe hydrogel was studied by treating rat skin trauma model. The results showed that compared with Comfeel® Plus Transparent dressing, the Tsg-THA&Fe hydrogel could obvious reduce the number of microorganisms, prevent bacterial colonization, reduce inflammation and accelerate wound healing. Local distribution of the Tsg-THA&Fe hydrogel in the skin tissue did not cause organ toxicity. Conclusions: In summary, the preparation process of Tsg-THA&Fe hydrogel is simple, with excellent performance in physical properties and biological efficacy. It can effectively relieve inflammation and control the colonization of wound microbes, and can be used as a multi-functional dressing to improve wound healing. [ABSTRACT FROM AUTHOR]

Liquid–liquid phase separation and related phase transitions have emerged as generic mechanisms in living cells for the formation of membraneless compartments or biomolecular condensates. The surface between two immiscible phases has an interfacial tension, generating capillary forces that can perform work on the surrounding environment. Here we present the physical principles of capillarity, including examples of how capillary forces structure multiphase condensates and remodel biological substrates. As with other mechanisms of intracellular force generation, for example, molecular motors, capillary forces can influence biological processes. Identifying the biomolecular determinants of condensate capillarity represents an exciting frontier, bridging soft matter physics and cell biology.The physical principles of capillarity, including how capillary forces can influence biological processes, are discussed. [ABSTRACT FROM AUTHOR]

Numerous organs in the bodies of animals, including the lung, kidney, and mammary gland, contain ramified networks of epithelial tubes. These structures arise during development via a process known as branching morphogenesis. Previous studies have shown that mechanical forces directly impact this process, but the patterns of mechanical stress exerted by branching embryonic epithelia are not well understood. This is, in part, owing to a lack of experimental tools. Traditional traction force microscopy assays rely on the use of compliant hydrogels with well-defined mechanical properties. Isolated embryonic epithelial explants, however, have only been shown to branch in three-dimensional matrices of reconstituted basement membrane protein, or Matrigel, a biomaterial with poorly characterized mechanical behavior, especially in the regime of large deformations. Here, to compute the traction stresses generated by branching epithelial explants, we quantified the finite-deformation constitutive behavior of gels of reconstituted basement membrane protein subjected to multi-axial mechanical loads. We then modified the mesenchyme-free assay for the ex vivo culture of isolated embryonic airway epithelial explants by suspending fluorescent microspheres within the surrounding gel and tracking their motion during culture. Surprisingly, the tracked bead motion was non-zero in regions of the gel far away from the explants, suggestive of passive swelling deformations within the matrix. To compute accurate traction stresses, these swelling deformations must be decomposed from those generated by the branching explants. We thus tracked the motion of beads suspended within cell-free matrices and quantified spatiotemporal patterns of gel swelling. Taken together, these passive swelling data can be combined with the measured mechanical properties of the gel to compute the traction forces exerted by intact embryonic epithelial explants. [ABSTRACT FROM AUTHOR]

Achieving fast and secure wound closure without ocular foreign body sensation is highly desired in ophthalmologic surgery. Sutureless approaches using tissue adhesives are gaining popularity, but their practical use is limited by the difficulty in controlling adhesion time and satisfying safety standards without compromising adhesive performance. Herein, we report user‐demand hydrogel‐forming ocular glues based on multilength photo‐crosslinkable hyaluronic acid (HA), achieving firm tissue adhesion under wet and dynamic conditions and possessing cornea‐like optical transparency. The HA‐based photocurable glue (HA photoglue) quickly seals wounds upon nontoxic low‐energy light exposure (320–500 nm, < 5 s, < 1 J cm−2), and its mechanical and adhesive properties are improved by introducing short and long crosslinkable moieties into HA through one‐step synthesis, forming multilength networks. Furthermore, the HA photoglue provides stable sealing in wet environments like ocular mucous surface, a clear vision with a light transmittance of more than 95% over the entire visible range, and a lubricating surface with minimal ocular sensation (generating less than 10% frictional force than suture groups). In a rabbit corneal incision model, the HA photoglue showed improved wound healing efficacy based on histological evaluation compared to control groups. [ABSTRACT FROM AUTHOR]

We discuss the formalism of chemical reaction networks (CRNs) as a computer-aided design interface for using formal methods in engineering living technologies. We set out by reviewing formal methods within a broader view of synthetic biology. Based on published results, we illustrate, step by step, how mathematical and computational techniques on CRNs can be used to study the structural and dynamic properties of the designed systems. As a case study, we use an E. coli two-component system that relays the external inorganic phosphate concentration signal to genetic components. We show how CRN models can scan and explore phenotypic regimes of synthetic promoters with varying detection thresholds, thereby providing a means for fine-tuning the promoter strength to match the specification., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Fibrosis is defined as the abnormal andexcessive depositionof extracellularmatrix (ECM) components, which leads to tissue or organ dysfunction and failure. However, the pathological mechanisms underlying fibrosis remain unclear. The inflammatory response induced by tissue injury is closely associated with tissue fibrosis. Recently, an increasing number of studies have linked necroptosis to inflammation and fibrosis. Necroptosis is a type of preprogrammed death caused by death receptors, interferons, Toll-like receptors, intracellular RNA and DNA sensors, and other mediators. These activate receptor-interacting protein kinase (RIPK) 1, which recruits and phosphorylates RIPK3. RIPK3 then phosphorylates a mixed lineage kinase domain-like protein and causes its oligomerization, leading to rapid plasmamembrane permeabilization, the release of cellular contents, and exposure of damage-associated molecular patterns (DAMPs). DAMPs, as inflammatory mediators, are involved in the loss of balance between extensive inflammation and tissue regeneration, leading to remodeling, the hallmark of fibrosis. In this review, we discuss the role of necroptotic DAMPs in tissue fibrosis and highlight the inflammatory responses induced by DAMPs in tissue ECM remodeling. By summarizing the existing literature on this topic, we underscore the gaps in the current research, providing a framework for future investigations into the relationship among necroptosis, DAMPs, and fibrosis, as well as a reference for later transformation into clinical treatment. [ABSTRACT FROM AUTHOR]

Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR) is an inherited disorder characterized by severe microcephaly and abnormal facial features. Kinesin family member 11 (KIF11) mutations have been reported closely related to microcephaly in different cases, while the pathogenicity was still unclear. Here, we report a de novo heterozygous mutation in exon 20 of the KIF11 (c.2922G>T; p.Pro974=) from a microcephaly patient through whole-exome sequencing. Further studies identified that this variant affected the normal splicing of KIF11 pre-mRNA, thus leading to the c.2815_2922 deletion of exon 20 through PBMC-derived pre-mRNA splicing assay and minigene experiment. Moreover, c.2815_2922 deletion would produce a shortened KIF11 protein, which may competitively bind to the normal KIF11 protein, suggesting a dominant negative effect mechanism in c.2922G>T mutation-induced MCLMR. [ABSTRACT FROM AUTHOR]