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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]

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]

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]

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]

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]

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]

A complete propagation of error procedure for passive microrheology is illustrated using synthetic data from generalized Brownian dynamics. Moreover, measurement errors typical of bead tracking done with laser interferometry are employed. We use the blocking transformation method of Flyvbjerg and Petersen (J Chem Phys 91(1):461–466 1989) applicable to estimating statistical uncertainty in autocorrelations for any time series data, to account properly for the correlation in the bead position data. These contributions to uncertainty in correlations have previously been neglected when calculating the error in the mean-squared displacement of the probe bead (MSD). The uncertainty in the MSD can be underestimated by a factor of about 20 if the correlation in the bead position data is neglected. Using the generalized Stokes-Einstein relation, the uncertainty in the MSD is then propagated to the dynamic modulus. Uncertainties in the bead radius and the trap stiffness are also taken into account. A simple code used to aid in the calculations is provided. [ABSTRACT FROM AUTHOR]

Like marine mussels, freshwater zebra and quagga mussels adhere via the byssus, a proteinaceous attachment apparatus. Attachment to various surfaces allows these invasive mussels to rapidly spread, however the adhesion mechanism is not fully understood. While marine mussel adhesion mechanics has been studied at the individual byssal-strand level, freshwater mussel adhesion has only been characterized through whole-mussel detachment, without direct interspecies comparisons on different substrates. Here, adhesive strength of individual quagga and zebra mussel byssal plaques were measured on smooth substrates with varying hydrophobicity—glass, PVC, and PDMS. With increased hydrophobicity of substrates, adhesive failures occurred more frequently, and mussel adhesion strength decreased. A new failure mode termed 'footprint failure' was identified, where failure appeared to be adhesive macroscopically, but a microscopic residue remained on the surface. Zebra mussels adhered stronger and more frequently on PDMS than quagga mussels. While their adhesion strengths were similar on PVC, there were differences in the failure mode and the plaque-substrate interface ultrastructure. Comparisons with previous marine mussel studies demonstrated that freshwater mussels adhere with comparable strength despite known differences in protein composition. An improved understanding of freshwater mussel adhesion mechanics may help explain spreading dynamics and will be important in developing effective antifouling surfaces. [ABSTRACT FROM AUTHOR]

Endothelin-1 (ET-1) is involved in the regulation of a myriad of processes highly relevant for physical and mental well-being; female and male health; in the modulation of senses, pain, stress reactions and drug sensitivity as well as healing processes, amongst others. Shifted ET-1 homeostasis may influence and predict the development and progression of suboptimal health conditions, metabolic impairments with cascading complications, ageing and related pathologies, cardiovascular diseases, neurodegenerative pathologies, aggressive malignancies, modulating, therefore, individual outcomes of both non-communicable and infectious diseases such as COVID-19. This article provides an in-depth analysis of the involvement of ET-1 and related regulatory pathways in physiological and pathophysiological processes and estimates its capacity as a predictor of ageing and related pathologies, a sensor of lifestyle quality and progression of suboptimal health conditions to diseases for their targeted prevention and as a potent target for cost-effective treatments tailored to the person. [ABSTRACT FROM AUTHOR]

Vanadocene dichloride (VDC), a vanadium containing metallocene dihalide exhibits promising anticancer activity. However, its mechanism of action remains elusive as several diverse targets and pathways have been proposed for its anticancer activity. In this study, we observed that VDC inhibited the proliferation of mammalian cancer cells and induced apoptotic cell death by altering the mitochondrial membrane potential and the expression of bcl2 and bax. Probing further into its anticancer mechanism, we found that VDC caused depolymerization of interphase microtubules and blocked the cells at mitosis with considerable proportion of cells exhibiting monopolar spindles. The reassembly of cold depolymerized microtubules was strongly inhibited in the presence of 10 μM VDC. VDC perturbed the microtubule-kinetochore interactions during mitosis as indicated by the absence of cold stable spindle microtubules in the cells treated with 20 μM VDC. Using goat brain tubulin, we found that VDC inhibited the steady-state polymer mass of microtubules and bound to tubulin at a novel site with a Kd of 9.71 ± 0.19 μM and perturbed the secondary structure of tubulin dimer. In addition, VDC was also found to bind to the mitotic kinesin Eg5 and inhibit its basal as well as microtubule stimulated ATPase activity. The results suggest that disruption of microtubule assembly dynamics and inhibition of the ATPase activity of Eg5 could be a plausible mechanism for the antiproliferative and antimitotic activity of VDC. Graphic abstract [ABSTRACT FROM AUTHOR]

Background: Seasonal flu is an infectious disease of the respiratory tract caused by influenza viruses. The development of anti-influenza drugs has significantly reduced the threat from the influenza virus; however, frequent mutations of this negative RNA virus result in antiviral-resistant strains, and constantly intimidate the human race. Thus, identifying novel therapeutic targets for the prevention and treatment of influenza virus infections is critical. Objective: We aimed to determine whether the kinesin superfamily protein 11 (KIF11) inhibitors, monastrol and K858, inhibit viral cytopathogenesis and influenza A virus (IAV) replication. Result: When MDCK or HEK293 cells were treated with monastrol and K858 that did not induce significant cytotoxicity, IAV-induced cytopathic effect was attenuated significantly. Furthermore, these inhibitors effectively suppressed the production of viral RNA, proteins, and infectious viral particles. Conclusion: Inhibition of KIF11 activity effectively attenuates virus-mediated cytopathic effect and suppresses viral replication. Hence, KIF11 is a potential therapeutic target against the influenza virus. [ABSTRACT FROM AUTHOR]

Fe cross-linked thermoplastic carboxylated nitrile butadiene rubber (XNBR) materials using Fe-COOH coordination as dynamic cross-links are reported. The transparent and brown Fe cross-linked XNBR (Fe/XNBR) elastomer was prepared by drying of Fe/XNBR organogels, which were fabricated by simple mixing of Fe3+ ethanol solution and XNBR dioxane solution. Tensile tests showed that only a small amount of Fe3+ ions (e.g., COOH/Fe=1/0.086, mol/mol) made the Fe/XNBR had even better tensile strength and stretchability than 2 phr sulphur vulcanized XNBR. Dynamic mechanical analysis demonstrated that the Fe-COOH interaction not only increased the moduli at higher temperatures, but also made the glass transition temperature high-temperature-shifted. In-situ infrared spectra measurements suggested that higher temperatures (e.g, 100°C) generated more trifunctional Fe-COOH cross-links and made the Fe-COOH interaction highly dynamic. The dynamic nature of the Fe-COOH interaction and generation of more trifunctional cross-links at high temperatures endowed fast self-healing and re-molding properties to the Fe/XNBR elastomers. Our result as a proof-of-concept illustrated a simple and cost-efficient way to fabricate self-healable thermoplastic elastomers using metal-ligand coordination in commercial rubbers. [ABSTRACT FROM AUTHOR]

Particle estimation is a classical problem arising in many science fields, such as biophysics, fluid mechanics and biomedical imaging. Many interesting applications in these areas involve 3D imaging data: This work presents a technique to estimate the 3D coordinates of the center of spherical particles. This procedure has its core in the processing of the images of the scanned volume: It firstly applies denoising techniques to each frame of the scanned volume and then provides an estimation of both the center and the profile of the 2D intersections of the particles with the frames, by coupling the usage of Total Variation functional and of a regularized weighted Least Squares fit. Then, the 2D information is used to retrieve the 3D coordinates using geometrical properties. The experiments provide evidence that image denoising has a large impact on the performance of the particle tracking procedures, since they strongly depend on the quality of the initial acquisition. This work shows that the choice of tailored image denoising technique for Poisson noise leads to a better estimation of the particle positions. [ABSTRACT FROM AUTHOR]

A mechanical model is presented to analyze the mechanics and dynamics of the cell cortex during indentation. We investigate the impact of active contraction on the cross-linked actin network for different probe sizes and indentation rates. The essential molecular mechanisms of filament stretching, cross-linking and motor activity, are represented by an active and viscous mechanical continuum. The filaments behave as worm-like chains linked either by passive rigid linkers or by myosin motors. In the first example, the effects of probe size and loading rate are evaluated using the model for an idealized rounded cell shape in which properties are based on the results of parallel-plate rheometry available in the literature. Extreme cases of probe size and indentation rate are taken into account. Afterward, AFM experiments were done by engaging smooth muscle cells with both sharp and spherical probes. By inverse analysis with finite element software, our simulations mimicking the experimental conditions show the model is capable of fitting the AFM data. The results provide spatiotemporal dependence on the size and rate of the mechanical stimuli. The model captures the general features of the cell response. It characterizes the actomyosin cortex as an active solid at short timescales and as a fluid at longer timescales by showing (1) higher levels of contraction in the zones of high curvature; (2) larger indentation forces as the probe size increases; and (3) increase in the apparent modulus with the indentation depth but no dependence on the rate of the mechanical stimuli. The methodology presented in this work can be used to address and predict microstructural dependence on the force generation of living cells, which can contribute to understanding the broad spectrum of results in cell experiments. [ABSTRACT FROM AUTHOR]

The magnetic tweezer technique has become a versatile tool for unfolding or folding of individual molecules, mainly DNA. In addition to single molecule analysis, the magnetic tweezer can be used to analyze the mechanical properties of cells and extracellular matrices. We have established a magnetic tweezer that is capable of measuring the linear and non-linear viscoelastic behavior of a wide range of soft matter in precisely controlled environmental conditions, such as temperature, CO2 and humidity. The magnetic tweezer presented in this study is suitable to detect specific differences in the mechanical properties of different cell lines, such as human breast cancer cells and mouse embryonic fibroblasts, as well as collagen matrices of distinct concentrations in the presence and absence of fibronectin crosslinks. The precise calibration and control mechanism employed in the presented magnetic tweezer setup provides the ability to apply physiological force up to 5 nN on 4.5 µm superparamagnetic beads coated with fibronectin and coupled to the cells or collagen matrices. These measurements reveal specific local linear and non-linear viscoelastic behavior of the investigated samples. The viscoelastic response of cells and collagen matrices to the force application is best described by a weak power law behavior. Our results demonstrate that the stress stiffening response and the fluidization of cells is cell type specific and varies largely between differently invasive and aggressive cancer cells. Finally, we showed that the viscoelastic behavior of collagen matrices with and without fibronectin crosslinks measured by the magnetic tweezer can be related to the microstructure of these matrices. [ABSTRACT FROM AUTHOR]

Stokes calculated the force exerted by the surrounding fluid on a sphere and on a cylinder in oscillating motion. Although these results are valid only if the Reynolds number Re is very small, Re ≪ 1 , all the tests on macroscopic spheres have been made with Re larger than 20. Here, we describe an experiment which measures the drag force on an oscillating sphere with small values of the Reynolds number, down to Re ≈ 0.03 for the smallest sphere studied here while the Stokes number St is large, between 150 and 1500. Our measurements are in very good agreement with Stokes' result, and in particular, they exhibit the quadratic dependence of the force with the sphere radius when this radius is larger than the viscous penetration depth δ . [ABSTRACT FROM AUTHOR]

Living cells are constantly exchanging momentum with their surroundings. So far, there is no consensus regarding how cells respond to such external stimuli, although it reveals much about their internal structures, motility as well as the emergence of disorders. Here, we report that twelve cell lines, ranging from healthy fibroblasts to cancer cells, hold a ubiquitous double power-law viscoelastic relaxation compatible with the fractional Kelvin-Voigt viscoelastic model. Atomic Force Microscopy measurements in time domain were employed to determine the mechanical parameters, namely, the fast and slow relaxation exponents, the crossover timescale between power law regimes, and the cell stiffness. These cell-dependent quantities show strong correlation with their collective migration and invasiveness properties. Beyond that, the crossover timescale sets the fastest timescale for cells to perform their biological functions. [ABSTRACT FROM AUTHOR]

The present paper reports the determination of the standard (p° = 0.1 MPa) molar enthalpy of formation in gas phase at T = 298.15 K of 3,5-dimethyl-4-nitroisoxazole, which was derived from the enthalpy of combustion in solid state and the sublimation enthalpy. The combustion enthalpy was derived from the respective combustion energy value, which was obtained from combustion calorimetry using a static bomb combustion calorimeter in oxygen atmosphere at T = 298.15 K. The sublimation enthalpy was obtained at the same temperature by using thermogravimetry experiments in isothermal regime. The purity and the constant pressure heat capacity of the compound were determined by using differential scanning calorimetry, priori to carry out the combustion experiments. The value obtained of formation enthalpy of compound in gas phase presents high precision and low uncertainty. [ABSTRACT FROM AUTHOR]

Evolution of eukaryotes from simple cells to complex multicellular organisms remains a mystery. Our postulate is that cytoskeletal stiffening is a necessary condition for evolution of complex multicellular organisms from early simple eukaryotes. Recent findings show that embryonic stem (ES) cells are as soft as primitive eukaryotes/amoebae and that differentiated tissue cells can be two orders of magnitude stiffer than ES cells. Soft ES cells become stiff as they differentiate into tissue cells of the complex multicellular organisms to match their microenvironment stiffness. We perhaps see in differentiation of ES cells (derived from inner cell mass cells) the echo of those early evolutionary events. Early soft unicellular organisms might have evolved to stiffen their cytoskeleton to protect their structural integrity from external mechanical stresses while being able to maintain form, to change shape, and to move. [ABSTRACT FROM AUTHOR]

Introduction: The brain is a very soft tissue. Glioblastoma (GBM) brain tumours are highly infiltrative into the surrounding healthy brain tissue and invasion mechanisms that have been defined using rigid substrates therefore may not apply to GBM dissemination. GBMs characteristically lose expression of the high molecular weight tropomyosins, a class of actin-associating proteins and essential regulators of the actin stress fibres and focal adhesions that underpin cell migration on rigid substrates.Methods: Here, we investigated how loss of the high molecular weight tropomyosins affects GBM on soft matrices that recapitulate the biomechanical architecture of the brain.Results: We find that Tpm 2.1 is down-regulated in GBM grown on soft substrates. We demonstrate that Tpm 2.1 depletion by siRNA induces cell spreading and elongation in soft 3D hydrogels, irrespective of matrix composition. Tpm 1.7, a second high molecular weight tropomyosin is also down-regulated when cells are cultured on soft brain-like surfaces and we show that effects of this isoform are matrix dependent, with Tpm 1.7 inducing cell rounding in 3D collagen gels. Finally, we show that the absence of Tpm 2.1 from primary patient-derived GBMs correlates with elongated, mesenchymal invasion.Conclusions: We propose that Tpm 2.1 down-regulation facilitates GBM colonisation of the soft brain environment. This specialisation of the GBM actin cytoskeleton organisation that is highly suited to the soft brain-like environment may provide novel therapeutic targets for arresting GBM invasion. [ABSTRACT FROM AUTHOR]

A method is presented to estimate the static error 휖 in a multiple particle tracking microrheology experiment. This in situ estimate of 휖 is measured under the same conditions of the material under test, and without any additional experiments. The correction of the mean-squared displacement by the in situ method is potentially more reliable than methods that rely on characterizing 휖 in a separate gel sample. With the true mean-squared displacements accessible at short lag times, experimental artifacts introduced by static error can be distinguished from true rheological properties, even in highly viscous (>10,000 mPa⋅s) samples. [ABSTRACT FROM AUTHOR]

Following the substantial progress in molecular simulations of polymer-matrix nanocomposites, now is the time to reconsider this topic from a critical point of view. A comprehensive survey is reported herein providing an overview of classical molecular simulations, reviewing their major achievements in modeling polymer matrix nanocomposites, and identifying several open challenges. Molecular simulations at multiple length and time scales, working hand-in-hand with sensitive experiments, have enhanced our understanding of how nanofillers alter the structure, dynamics, thermodynamics, rheology and mechanical properties of the surrounding polymer matrices. [ABSTRACT FROM AUTHOR]

Quasi-one-dimensional microtubules (MTs) in cells enjoy high axial rigidity but large transverse flexibility due to the inter-protofilament (PF) sliding. This study aims to explore the structure-property relation for MTs and examine the relevance of the beam theories to their unique features. A molecular structural mechanics (MSM) model was used to identify the origin of the inter-PF sliding and its role in bending and vibration of MTs. The beam models were then fitted to the MSM to reveal how they cope with the distinct mechanical responses induced by the inter-PF sliding. Clear evidence showed that the inter-PF sliding is due to the soft inter-PF bonds and leads to the length-dependent bending stiffness. The Euler beam theory is found to adequately describe MT deformation when the inter-PF sliding is largely prohibited. Nevertheless, neither shear deformation nor the nonlocal effect considered in the ‘more accurate’ beam theories can fully capture the effect of the inter-PF sliding. This reflects the distinct deformation mechanisms between an MT and its equivalent continuous body. [ABSTRACT FROM AUTHOR]

We present a new method for performing passive probe microrheology. Using a simple theoretical framework, we show how probes' mean-squared displacements can be extracted by analyzing intensity fluctuations in optical microscopy videos via differential dynamic microscopy (DDM). Applying the method to optically dilute probes in Newtonian and viscoelastic fluids quantitatively reproduces mean-squared displacements extracted from multiple particle tracking (MPT), and exposes the relative strengths and weakness of DDM. Furthermore, DDM can be used to measure the mean-squared displcement in optically dense fluids where MPT fails, demonstrating that DDM can extend the range of microrheology experiments while circumventing many of the drawbacks of MPT. [ABSTRACT FROM AUTHOR]

Diffuse invasion of glioma cells into the brain parenchyma leads to nonresectable brain tumors and poor prognosis of glioma disease. In vivo, glioma cells can adopt a range of invasion strategies and routes, by moving as single cells, collective strands and multicellular networks along perivascular, perineuronal and interstitial guidance cues. Current in vitro assays to probe glioma cell invasion, however, are limited in recapitulating the modes and adaptability of glioma invasion observed in brain parenchyma, including collective behaviours. To mimic in vivo-like glioma cell invasion in vitro, we here applied three tissue-inspired 3D environments combining multicellular glioma spheroids and reconstituted microanatomic features of vascular and interstitial brain structures. Radial migration from multicellular glioma spheroids of human cell lines and patient-derived xenograft cells was monitored using (1) reconstituted basement membrane/hyaluronan interfaces representing the space along brain vessels; (2) 3D scaffolds generated by multi-layered mouse astrocytes to reflect brain interstitium; and (3) freshly isolated mouse brain slice culture ex vivo. The invasion patterns in vitro were validated using histological analysis of brain sections from glioblastoma patients and glioma xenografts infiltrating the mouse brain. Each 3D assay recapitulated distinct aspects of major glioma invasion patterns identified in mouse xenografts and patient brain samples, including individually migrating cells, collective strands extending along blood vessels, and multicellular networks of interconnected glioma cells infiltrating the neuropil. In conjunction, these organotypic assays enable a range of invasion modes used by glioma cells and will be applicable for mechanistic analysis and targeting of glioma cell dissemination. [ABSTRACT FROM AUTHOR]

A molecular structural mechanics (MSM) method has been implemented to investigate the free vibration of microtubules (MTs). The emphasis is placed on the effects of the configuration and the imperfect boundaries of MTs. It is shown that the influence of protofilament number on the fundamental frequency is strong, while the effect of helix-start number is almost negligible. The fundamental frequency is also found to decrease as the number of the blocked filaments at boundaries decreases. Subsequently, the Euler-Bernoulli beam theory is employed to reveal the physics behind the simulation results. Fitting the Euler-Bernoulli beam into the MSM data leads to an explicit formula for the fundamental frequency of MTs with various configurations and identifies a possible correlation between the imperfect boundary conditions and the length-dependent bending stiffness of MTs reported in experiments. [ABSTRACT FROM AUTHOR]

Inherited afibrinogenemia and hypofibrinogenemia are rare bleeding disorders characterized by markedly reduced levels of fibrinogen in blood. Thrombotic complications in these disorders have been rarely described. We performed a multicenter retrospective study and reviewed the occurrence of thrombotic complications among patients with inherited fibrinogen deficiency. Cases were identified during a review of medical records of all patients with inherited fibrinogen deficiency followed at three different university hospitals in Israel. Nine patients were included in this study: five were afibrinogenemic and four hypofibrinogenemic. There were seven thrombotic events, mostly venous, that occurred in four out of nine patients (44 %). All thrombotic events occurred in afibrinogenemic patients. Mean age at the time of thrombosis was 45 (range 28-61) years. Thrombophilic evaluation performed was negative in all cases. At the time of thrombosis in five out of seven (71.4 %) events, fibrinogen replacement therapy was concurrently given. Therapeutic approach was different among patients ranging from supportive therapy alone, antiplatelet agents and anticoagulant therapy with the concurrent administration of fibrinogen replacement therapy. This study discloses a high rate of thrombosis in patients with afibrinogenemia. Events were both venous and arterial and may be recurrent. Management is highly problematic due to the precarious balance between bleeding and thrombotic risk in these patients. Fibrinogen replacement therapy should be cautiously used in these patients as most thrombotic events followed the administration of fibrinogen replacement therapy. Larger cohorts are warranted to better characterize the best management strategy in these paradoxical events. [ABSTRACT FROM AUTHOR]

In situ dynamics of colloidal cluster formation from nanoparticles is yet to be addressed. Using two-photon fluorescence (TPF) that has been amply used for single particle tracking, we demonstrate in situ measurement of effective three-dimensional optical trap stiffness of nanoparticles and their aggregates without using any position sensitive detector. Optical trap stiffness is an essential measure of the strength of an optical trap. TPF is a zero-background detection scheme and has excellent signal-to-noise-ratio, which can be easily extended to study the formation of colloidal cluster of nanospheres in the optical trapping regime. TPF tracking can successfully distinguish colloidal cluster from its monomer. [ABSTRACT FROM AUTHOR]

Actomyosin stress fibers, one of the main components of the cell's cytoskeleton, provide mechanical stability to adherent cells by applying and transmitting tensile forces onto the extracellular matrix (ECM) at the sites of cell-ECM adhesion. While it is widely accepted that changes in spatial and temporal distribution of stress fibers affect the cell's mechanical properties, there is no quantitative knowledge on how stress fiber amount and organization directly modulate cell stiffness. We address this key open question by combining atomic force microscopy with simultaneous fluorescence imaging of living cells, and combine for the first time reliable quantitative parameters obtained from both techniques. We show that the amount of myosin and (to a lesser extent) actin assembled in stress fibers directly modulates cell stiffness in adherent mouse fibroblasts (NIH3T3). In addition, the spatial distribution of stress fibers has a second-order modulatory effect. In particular, the presence of either fibers located in the cell periphery, aligned fibers or thicker fibers gives rise to reinforced cell stiffness. Our results provide basic and significant information that will help design optimal protocols to regulate the mechanical properties of adherent cells via pharmacological interventions that alter stress fiber assembly or via micropatterning techniques that restrict stress fiber spatial organization. [ABSTRACT FROM AUTHOR]

The rheological properties of fibrin networks have been of long-standing interest. As such there is a wealth of studies of their shear and tensile responses, but their compressive behavior remains unexplored. Here, by characterization of the network structure with synchronous measurement of the fibrin storage and loss moduli at increasing degrees of compression, we show that the compressive behavior of fibrin networks is similar to that of cellular solids. A nonlinear stress-strain response of fibrin consists of three regimes: (1) an initial linear regime, in which most fibers are straight, (2) a plateau regime, in which more and more fibers buckle and collapse, and (3) a markedly nonlinear regime, in which network densification occurs by bending of buckled fibers and inter-fiber contacts. Importantly, the spatially non-uniform network deformation included formation of a moving 'compression front' along the axis of strain, which segregated the fibrin network into compartments with different fiber densities and structure. The Young's modulus of the linear phase depends quadratically on the fibrin volume fraction while that in the densified phase depends cubically on it. The viscoelastic plateau regime corresponds to a mixture of these two phases in which the fractions of the two phases change during compression. We model this regime using a continuum theory of phase transitions and analytically predict the storage and loss moduli which are in good agreement with the experimental data. Our work shows that fibrin networks are a member of a broad class of natural cellular materials which includes cancellous bone, wood and cork. [ABSTRACT FROM AUTHOR]

Molecular motors are enzymes that convert chemical potential energy into controlled kinetic energy for mechanical work inside cells. Understanding the biophysics of these motors is essential for appreciating life as well as apprehending diseases that arise from motor malfunction. This review focuses on kinesin motor enzymology with special emphasis on the literature that reports the chemistry, structure and physics of several different kinesin superfamily members. [ABSTRACT FROM AUTHOR]

Pathological accumulation of the microtubule-associated protein tau, in the form of neurofibrillary tangles, is a major hallmark of Alzheimer's disease, the most prevalent neurodegenerative condition worldwide. In addition to Alzheimer's disease, a number of neurodegenerative diseases, called tauopathies, are characterized by the accumulation of aggregated tau in a variety of brain regions. While tau normally plays an important role in stabilizing the microtubule network of the cytoskeleton, its dissociation from microtubules and eventual aggregation into pathological deposits is an area of intense focus for therapeutic development. Here we discuss the known cellular factors that affect tau aggregation, from post-translational modifications to molecular chaperones. [ABSTRACT FROM AUTHOR]