Search

Cells cultured on stiff 2D substrates exert high intracellular force, resulting in mechanical deformation of their nuclei. This nuclear deformation (ND) plays a crucial role in the transport of Yes Associated Protein (YAP) from the cytoplasm to the nucleus. However, cells in vivo are in soft 3D environment with potentially much lower intracellular forces. Whether and how cells may deform their nuclei in 3D for YAP localization remains unclear. Here, by culturing human colon cancer associated fibroblasts (CAFs) on 2D, 2.5D, and 3D substrates, we differentiated the effects of stiffness, force, and ND on YAP localization. We found that nuclear translocation of YAP depends on the degree of ND irrespective of dimensionality, stiffness and total force. ND induced by the perinuclear force, not the total force, and nuclear membrane curvature correlate strongly with YAP activation. Immunostained slices of human tumors further supported the association between ND and YAP nuclear localization, suggesting ND as a potential biomarker for YAP activation in tumors. Additionally, we conducted quantitative analysis of the force dynamics of CAFs on 2D substrates to construct a stochastic model of YAP kinetics. This model revealed that the probability of YAP nuclear translocation, as well as the residence time in the nucleus follow a power law. This study provides valuable insights into the regulatory mechanisms governing YAP dynamics and highlights the significance of threshold activation in YAP localization. Yes Associated Protein (YAP), a transcription cofactor, has been identified as one of the drivers of cancer progression. High tumor stiffness is attributed to driving YAP to the nucleus, wherein it activates pro-metastatic genes. Here we show, using cancer associated fibroblasts, that YAP translocation to the nucleus depends on the degree of nuclear deformation, irrespective of stiffness. We also identified that perinuclear force induced membrane curvature correlates strongly with YAP nuclear transport. A novel stochastic model of YAP kinetics unveiled a power law relationship between the activation threshold and persistence time of YAP in the nucleus. Overall, this study provides novel insights into the regulatory mechanisms governing YAP dynamics and the probability of activation that is of immense clinical significance. [Display omitted] [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The defense mechanism of hagfish slime is remarkable considering that hagfish cannot control the concentration of the resulting gel directly; they simply exude a concentrated material into a comparably "infinite" sea of water to form a dilute, sticky, cohesive elastic gel. This raises questions about the robustness of gel formation and rheological properties across a range of concentrations, which we study here for the first time. Across a nearly 100-fold change in concentration, we discover that the gel has similar viscoelastic time-dependent properties with constant power-law exponent (α = 0.18 ± 0.01), constant relative damping tan δ = G ′′ / G ′ ≈ 0.2 – 0.3 , and varying overall stiffness that scales linearly with the concentration (∼ c 0.99 ± 0.05 ). The power-law viscoelasticity (fit by a fractional Kelvin-Voigt model) is persistent at all concentrations with nearly constant fractal dimension. This is unlike other materials and suggests that the underlying material structure of slime remains self-similar irrespective of concentration. This interpretation is consistent with our microscopy studies of the fiber network. We derive a structure-rheology model to test the hypothesis that the origins of ultra-soft elasticity are based on bending of the fibers. The model predictions show an excellent agreement with the experiments. Our findings illustrate the unusual and robust properties of slime which may be vital in its physiological use and provide inspiration for the design of new engineered materials. Statement of Significance Hagfish produce a unique gel-like material to defend themselves against predator attacks. The successful use of the defense gel is remarkable considering that hagfish cannot control the concentration of the resulting gel directly; they simply exude a small quantity of biomaterial which then expands by a factor of 10,000 (by volume) into an "infinite" sea of water. This raises questions about the robustness of gel formation and properties across a range of concentrations. This study provides the first ever understanding of the mechanics of hagfish slime over a very wide range of concentration. We discover that some viscoelastic properties of slime are remarkably constant regardless of its concentration. Such a characteristic is uncommon in most known materials. [ABSTRACT FROM AUTHOR]

Surface texturing can decrease friction in lubricated sliding contact. The majority of existing experimental work has focused on symmetric-depth-profile surface textures. This experimental work examines asymmetric-depth-profile surface textures using gap-controlled experiments with Newtonian fluids on a custom tribo-rheometer setup. Measurements of normal force and shear load are reported as a function of texture geometry, gap height, and bi-directional sliding velocity. This work shows that, in the absence of cavitation, surface texture depth symmetry must be broken to produce normal forces (through viscous effects) for gap-based Reynolds Number up to Re h = ρ V h η = 1.21 . Asymmetric surface textures reduce shear stress and generate normal load, and therefore decrease the effective friction coefficient, which we observe to be smallest for the shallowest texture angle tested, β =5.3°. [ABSTRACT FROM AUTHOR]

Abstract: We report here the first experimental measurements of non-linear rheological material properties of hagfish slime, a hydrated biopolymer/biofiber network, and develop a microstructural constitutive model to explain the observed non-linear viscoelastic behavior. The linear elastic modulus of the network is observed to be for timescales , making it one of the softest elastic biomaterials known. Non-linear rheology is examined via simple shear deformation, and we observe a secant elastic modulus which strain-softens at large input strain while the local tangent elastic modulus strain-stiffens simultaneously. This juxtaposition of simultaneous softening and stiffening suggests a general network structure composed of non-linear elastic strain-stiffening elements, here modeled as finite extensible non-linear elastic (FENE) springs, in which network connections are destroyed as elements are stretched. We simulate the network model in oscillatory shear and creep, including instrument effects from rotational inertia. The network model captures the simultaneous softening of the secant modulus and stiffening of tangent modulus as the model enters the non-linear viscoelastic regime. [Copyright &y& Elsevier]

Abstract Fresh concrete is often cited as an example of a yield-stress fluid, typically being modeled as a Bingham material. We describe how this is an incomplete understanding to rationalize simple but important flow behaviors. As a motivating phenomenon, we consider the practice of vibrating fresh concrete during placement to induce flow and remove air voids. It is demonstrated that a simple yield-stress fluid (an aqueous polymer microgel particle suspension, Carbopol) cannot recreate the phenomenon, falsifying the hypothesis that traditional yield-stress fluid models embody the key physics. However, a granular hard-particle suspension (millimetric glass beads in silicone oil) does recreate the phenomenon. We use shear rheology to further show that concrete displays noticeable granular physics as indicated by vibration-induced loss of the yield stress, consistent with the granular constitutive model of Hanotin et al. (2015). These results have implications for understanding the unseen phenomenon of air bubbles rising in concrete. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cells (HSC) reside in unique bone marrow niches and are influenced by signals from surrounding cells, the extracellular matrix (ECM), ECM-bound or diffusible biomolecules. Here we describe the use of a three-dimensional hydrogel to alter the balance of HSC-generated autocrine feedback and paracrine signals generated by co-cultured niche-associated cells. We report shifts in HSC proliferation rate and fate specification in the presence of lineage positive (Lin + ) niche cells. Hydrogels promoting autocrine feedback enhanced expansion of early hematopoietic progenitors while paracrine signals from Lin + cells increased myeloid differentiation. We report thresholds where autocrine vs. paracrine cues alter HSC fate transitions, and were able to selectively abrogate the effects of matrix diffusivity and niche cell co-culture via the use of inhibitory cocktails of autocrine or paracrine signals. Together, these results suggest diffusive biotransport in three-dimensional biomaterials are a critical design element for the development of a synthetic stem cell niche. [ABSTRACT FROM AUTHOR]

Frontal polymerization (FP) is an efficient method to manufacture thermoset polymers and composites, and is usually modeled as a reaction–diffusion (RD) process. In this study, we investigate numerically and experimentally how fluid convection ahead of the propagating front can impact the reaction–diffusion balance in the free-surface FP of dicyclopentadiene (DCPD) and 5-ethylidene-2-norbornene (ENB). Multiphysics finite element analyses reveal how the velocity of the surface-tension-driven flow described by the dimensionless Marangoni number can be modulated by varying the processing temperature and the viscosity of the monomer resin. The surface-tension-driven fluid velocity exhibits two distinct regimes, which arise from the interplay and competition between thermal and chemical advection. The dispersion of the reaction heat by the Marangoni flow leads to a reduction in the velocity of the front. The presence of fluid convection during FP can lead to instabilities in the front propagation and generate reaction patterns, which can be adjusted by controlling the initial temperature and degree of cure. The numerical findings are corroborated by experiments that combine FP and particle image velocimetry (PIV). • We establish a multiphysics model for frontal polymerization with Marangoni flow. • Marangoni flow can reduce the front velocity and affect the front shape. • Marangoni flow can trigger instabilities of frontal polymerization. • The initial temperature and degree of cure can adjust instabilities. • Simulations and experiments yield a high level of agreement. [ABSTRACT FROM AUTHOR]

Microtextured surfaces can reduce friction in lubricated dynamic contact. However, no prior experimental study has explored the dimensionless parameter space of Reynolds number and dimensionless gap, since normal force is easier to control than the fluid film thickness. Here, we develop a custom precision-aligned setup for gap-controlled tribo-rheometry based on a rotational rheometer. The novel experimental setup allows for measurement of full film lubrication of parallel disks down to 20 μm gaps with gap precision ±3 μm, over a range of Reynolds numbers. We show for the first time in gap-controlled conditions that microtextured surfaces reduce friction. The reduction in dimensionless shear stress is nearly independent of velocity for Re <10 which matches computational results in this work. [ABSTRACT FROM AUTHOR]

Large amplitude oscillatory shear stress (LAOStress) was used to study the nonlinear rheological properties of Afuega'l Pitu (PDO) cheese atroncau blancu and roxu , a Spanish acid-curd cheese made from cow's milk, from nine manufacturers. Composition, physicochemical and lipolytic parameters were determined. The moisture content varied between (23.60 ± 0.75)% and (45.84 ± 0.01)% and the percentage of salt-in-moisture was < (8.17 ± 0.86)%. Stress amplitude sweeps were conducted at 20 °C, 50 °C and 75 °C at frequencies of 0.628 rad/s, 6.28 rad/s and 31.4 rad/s, for each temperature. Experiments were analyzed using the MITlaos software modified to extract LAOStress quantitative material functions. The large number of experiments and the high dimensionality of the LAOS signals were carefully analyzed and reduced to understand the material response and extract the relevant properties. All cheeses showed a distinct signature that motivates us to introduce the concept of "pseudo-linear LAOS" where nonlinear rheology is evident in only some measures while others minimally change from the linear regime. We geometrically interpret these different LAOS measures as rotation and distortion of Lissajous curves; all cheeses showed pseudo-linear LAOS regimes where rotation is strong and distortion is minimal, i.e. first-harmonics change dramatically in a regime where higher-harmonics are small enough that Lissajous curves are nearly elliptical. The pseudo-linear behavior enabled low-dimensional data reduction and three metrics were discovered to be the most relevant: linear elastic modulus (G ′), critical stress (σ crit) and strain (γ crit) amplitudes. All Afuega'l Pitu cheese samples softened as stress amplitude increased while maintaining a solid-like behavior (tan δ ^ 1 ∼ 0.3), regardless of frequency and temperature. Moreover, the difference between blancu and roxu was statistically insignificant compared to difference between manufacturers. Linear G ′ and nonlinear σ crit decreased with increasing temperature, while the nonlinear γ crit maintained a constant value at 50 °C and 75 °C. Although G ′, σ crit and γ crit metrics establish comparison between cheeses, more metrics are still required to fully connect rheology to cheese texture and sensory profiles. [Display omitted] • First LAOS study on an acid-curd cheese. • Pseudo-linear LAOS response simplifies analysis. • Reduced LAOS data to only three quantitative metrics: G ′, σ crit and γ crit. • G ′, σ crit decreased with moisture content while γ crit showed no clear correlation. • Differences between blancu and roxu are smaller than between nine individual manufacturers. [ABSTRACT FROM AUTHOR]

The purpose of this of study was to investigate the confined vibration method to produce alumina beads for the study of stress wave propagation in granular media. The method produces beads with desirable shape (i.e. oblate, prolate, and tri-axial ellipsoid), microstructure (level of porosity), and size (5 mm to 3 cm in diameter). This environmentally friendly approach to process beads involves preparing a slurry with a small amount of PVA binder and dispersant. After drying, the pre-formed material is a shear-reversible soft-solid, which flows under applied stress with limited strain recovery. This rheological behavior is sufficient for the alumina paste to be processed into rounded shapes with a confined shaker table and to maintain the shape for sintering of the alumina beads. [ABSTRACT FROM AUTHOR]

Abstract: Dynamic oscillatory shear tests are common in rheology and have been used to investigate a wide range of soft matter and complex fluids including polymer melts and solutions, block copolymers, biological macromolecules, polyelectrolytes, surfactants, suspensions, emulsions and beyond. More specifically, small amplitude oscillatory shear (SAOS) tests have become the canonical method for probing the linear viscoelastic properties of these complex fluids because of the firm theoretical background and the ease of implementing suitable test protocols. However, in most processing operations the deformations can be large and rapid: it is therefore the nonlinear material properties that control the system response. A full sample characterization thus requires well-defined nonlinear test protocols. Consequently there has been a recent renewal of interest in exploiting large amplitude oscillatory shear (LAOS) tests to investigate and quantify the nonlinear viscoelastic behavior of complex fluids. In terms of the experimental input, both LAOS and SAOS require the user to select appropriate ranges of strain amplitude (γ 0) and frequency (ω). However, there is a distinct difference in the analysis of experimental output, i.e. the material response. At sufficiently large strain amplitude, the material response will become nonlinear in LAOS tests and the familiar material functions used to quantify the linear behavior in SAOS tests are no longer sufficient. For example, the definitions of the linear viscoelastic moduli G′(ω) and G″(ω) are based inherently on the assumption that the stress response is purely sinusoidal (linear). However, a nonlinear stress response is not a perfect sinusoid and therefore the viscoelastic moduli are not uniquely defined; other methods are needed for quantifying the nonlinear material response under LAOS deformation. In the present review article, we first summarize the typical nonlinear responses observed with complex fluids under LAOS deformations. We then introduce and critically compare several methods that quantify the nonlinear oscillatory stress response. We illustrate the utility and sensitivity of these protocols by investigating the nonlinear response of various complex fluids over a wide range of frequency and amplitude of deformation, and show that LAOS characterization is a rigorous test for rheological models and advanced quality control. [Copyright &y& Elsevier]

Abstract: Here we develop an injectable composite system based for repeated ultrasound-triggered on-demand drug delivery. An in situ-cross-linking hydrogel maintains model drug (dye)-containing liposomes in close proximity to gas-filled microbubbles that serve to enhance release events induced by ultrasound application. Dye release is tunable by varying the proportions of the liposomal and microbubble components, as well as the duration and intensity of the ultrasound pulses in vitro. Dye is minimal at baseline. The composite shows minimal cytotoxicity in vitro, and benign tissue reaction after subcutaneous injection in rats. Ultrasound application also triggers drug release for two weeks after injection in vivo. [Copyright &y& Elsevier]

• Categorizes "design with" versus "design of" rheologically-complex materials. • Considers "How many ways to get a yield-stress fluid?" • Considers "Can we predict properties from formulation and structure?" • Considers "How to transform a yield-stress fluid to be more useful?" • Future research directions are suggested to build the toolbox of design. We review progress in designing and transforming multi-functional yield-stress fluids and give a perspective on the current state of knowledge that supports each step in the design process. We focus mainly on the rheological properties that make yield-stress fluids so useful and the trade-offs which need to be considered when working with these materials. Thinking in terms of "design with" and "design of" yield-stress fluids motivates how we can organize our scientific understanding of this field. "Design with" involves identification of rheological property requirements independent of the chemical formulation, e.g. for 3D direct-write printing which needs to accommodate a wide range of chemistry and material structures. "Design of" includes microstructural considerations: conceptual models relating formulation to properties, quantitative models of formulation-structure-property relations, and chemical transformation strategies for converting effective yield-stress fluids to be more useful solid engineering materials. Future research directions are suggested at the intersection of chemistry, soft-matter physics, and material science in the context of our desire to design useful rheologically-complex functional materials. [ABSTRACT FROM AUTHOR]