Ultrafast Axial Freezing in a Liquid-Filled Capillary Tube.

Liquid-filled capillary tubes are a kind of standard component in life science (e.g., blood vessels, interstitial pores, and plant vessels) and engineering (e.g., MEMS microchannel resonators, heat pipe wicks, and water-saturated soils). Under sufficiently low temperatures, the liquid in a capillary tube undergoes phase transition, forming an ice nucleus randomly on its inner wall. However, how an ice layer forms from the nucleus and then expands, either axially or radially to the tube inner wall, remains obscure. We demonstrated, both experimentally and theoretically, that axial freezing along the inner wall of a water-filled capillary tube occurs way ahead of radial freezing, at a nearly constant velocity 3 orders in magnitude faster than the latter. Rapid release of latent heat during axial freezing was identified as the determining factor for the short duration of recalescence, resulting in an exponential rise of the supercooling temperature from ice nucleation via axial freezing to radial freezing. The profile of the ice-water interface is strongly dependent upon the length-to-radius ratio of the capillary tube and the supercooling degree at ice nucleation. The results obtained in this study bridge the knowledge gap between the classical nucleation theory and the Stefan solution of phase transition.

Directed cell migration towards softer environments.

How cells sense tissue stiffness to guide cell migration is a fundamental question in development, fibrosis and cancer. Although durotaxis-cell migration towards increasing substrate stiffness-is well established, it remains unknown whether individual cells can migrate towards softer environments. Here, using microfabricated stiffness gradients, we describe the directed migration of U-251MG glioma cells towards less stiff regions. This 'negative durotaxis' does not coincide with changes in canonical mechanosensitive signalling or actomyosin contractility. Instead, as predicted by the motor-clutch-based model, migration occurs towards areas of 'optimal stiffness', where cells can generate maximal traction. In agreement with this model, negative durotaxis is selectively disrupted and even reversed by the partial inhibition of actomyosin contractility. Conversely, positive durotaxis can be switched to negative by lowering the optimal stiffness by the downregulation of talin-a key clutch component. Our results identify the molecular mechanism driving context-dependent positive or negative durotaxis, determined by a cell's contractile and adhesive machinery.

Acoustic radiation force on a long cylinder, and potential sound transduction by tomato trichomes.

Acoustic transduction by plants has been proposed as a mechanism to enable just-in-time up-regulation of metabolically expensive defensive compounds. Although the mechanisms by which this "hearing" occurs are unknown, mechanosensation by elongated plant hair cells known as trichomes is suspected. To evaluate this possibility, we developed a theoretical model to evaluate the acoustic radiation force that an elongated cylinder can receive in response to sounds emitted by animals, including insect herbivores, and applied it to the long, cylindrical stem trichomes of the tomato plant Solanum lycopersicum. Based on perturbation theory and validated by finite element simulations, the model quantifies the effects of viscosity and frequency on this acoustic radiation force. Results suggest that acoustic emissions from certain animals, including insect herbivores, may produce acoustic radiation force sufficient to trigger stretch-activated ion channels.

A new model of myofibroblast-cardiomyocyte interactions and their differences across species.

Although coupling between cardiomyocytes and myofibroblasts is well known to affect the physiology and pathophysiology of cardiac tissues across species, relating these observations to humans is challenging because the effect of this coupling varies across species and because the sources of these effects are not known. To identify the sources of cross-species variation, we built upon previous mathematical models of myofibroblast electrophysiology and developed a mechanoelectrical model of cardiomyocyte-myofibroblast interactions as mediated by electrotonic coupling and transforming growth factor-ß1. The model, as verified by experimental data from the literature, predicted that both electrotonic coupling and transforming growth factor-ß1 interaction between myocytes and myofibroblast prolonged action potential in rat myocytes but shortened action potential in human myocytes. This variance could be explained by differences in the transient outward K+ current associated with differential Kv4.2 gene expression across species. Results are useful for efforts to extrapolate the results of animal models to the predicted effects in humans and point to potential therapeutic targets for fibrotic cardiomyopathy.

Janus Vitrification of Droplet via Cold Leidenfrost Phenomenon.

Janus particles with asymmetric crystals show great importance in optoelectronics and photocatalysis, but their synthesis usually requires complicated procedures. Here, an unexpected Janus vitrification phenomenon is observed in a droplet caused by the Leidenfrost effect at a cryogenic temperature, which is commonly regarded as symmetric. The Leidenfrost phenomenon levitates the droplet when it comes in contact with liquid nitrogen causing different cooling conditions on the droplet's top and bottom surfaces. It induces asymmetric crystallization in the droplet, forming a Janus vitrified particle with an asymmetric crystallization borderline after cooling, as further evidenced by cryotransmission electron microscopy (cryo-TEM) experiments. Theoretical analysis and experimental study indicate that the position of the asymmetric crystallization borderline is determined by the droplet radius and density, and the observation window of asymmetric crystallization borderline is determined by the chemical concentration. The finding reveals the asymmetric crystallization phenomenon in droplet vitrification for the first time, and provides a new insight for creating Janus particles through the Leidenfrost phenomenon.

Anomalous Loss of Stiffness with Increasing Reinforcement in a Photo-Activated Nanocomposite.

Hydrogels are commonly doped with stiff nanoscale fillers to endow them with the strength and stiffness needed for engineering applications. Although structure-property relations for many polymer matrix nanocomposites are well established, modeling the new generation of hydrogel nanocomposites requires the study of processing-structure-property relationships because subtle differences in chemical kinetics during their synthesis can cause nearly identical hydrogels to have dramatically different mechanical properties. The authors therefore assembled a framework to relate synthesis conditions (including hydrogel and nanofiller mechanical properties and light absorbance) to gelation kinetics and mechanical properties. They validated the model against experiments on a graphene oxide (GO) doped oligo (ethylene glycol) diacrylate (OEGDA), a system in which, in apparent violation of laws from continuum mechanics, doping can reduce rather than increase the stiffness of the resulting hydrogel nanocomposites. Both model and experiment showed a key role light absorbance-dominated gelation kinetics in determining nanocomposite mechanical properties in conjunction with nanofiller reinforcement, with the nanofiller's attenuation of chemical kinetics sometimes outweighing stiffening effects to explain the observed, anomalous loss of stiffness. By bridging the chemical kinetics and mechanics of nanocomposite hydrogels, the authors' modeling framework shows promise for broad applicability to design of hydrogel nanocomposites.

Spatiotemporally Controlled Photoresponsive Hydrogels: Design and Predictive Modeling from Processing through Application.

Photoresponsive hydrogels (PRHs) are soft materials whose mechanical and chemical properties can be tuned spatially and temporally with relative ease. Both photo-crosslinkable and photodegradable hydrogels find utility in a range of biomedical applications that require tissue-like properties or programmable responses. Progress in engineering with PRHs is facilitated by the development of theoretical tools that enable optimization of their photochemistry, polymer matrices, nanofillers, and architecture. This review brings together models and design principles that enable key applications of PRHs in tissue engineering, drug delivery, and soft robotics, and highlights ongoing challenges in both modeling and application.

Characterizing poroelasticity of biological tissues by spherical indentation: an improved theory for large relaxation.

Flow of fluids within biological tissues often meets with resistance that causes a rate- and size-dependent material behavior known as poroelasticity. Characterizing poroelasticity can provide insight into a broad range of physiological functions, and is done qualitatively in the clinic by palpation. Indentation has been widely used for characterizing poroelasticity of soft materials, where quantitative interpretation of indentation requires a model of the underlying physics, and such existing models are well established for cases of small strain and modest force relaxation. We showed here that existing models are inadequate for large relaxation, where the force on the indenter at a prescribed depth at long-time scale drops to below half of the initially peak force (i.e., F(0)/F(∞) > 2). We developed an indentation theory for such cases of large relaxation, based on Biot theory and a generalized Hertz contact model. We demonstrated that our proposed theory is suitable for biological tissues (e.g., spleen, kidney, skin and human cirrhosis liver) with both small and large relaxations. The proposed method would be a powerful tool to characterize poroelastic properties of biological materials for various applications such as pathological study and disease diagnosis.

Sound absorption theory for micro-perforated panel with petal-shaped perforations.

Micro-perforated panel (MPP) absorbers with circular perforations are used in many noise control applications due to their attractive wide-brand sound absorption performance. Different from a common MPP with circular perforations, a unique type of MPP absorber with petal-shaped perforations is proposed. The sound absorption theory for the MPP with petal-shaped perforations is developed by accurately considering the fluid velocity in the petal-shaped perforation hole. This theory can account for the effect of altered perforation morphology (from circular to petal) on sound absorption. Finite element simulations are performed to validate the proposed theory, with good agreement achieved. The sound absorption of MPP with petal-shaped perforations is compared with that of the traditional MPP with the same porosity. It is demonstrated that the change in hole shape significantly modifies the fluid velocity field and the flow resistivity in/of the hole, and hence the sound absorption of the proposed MPP with petal-shaped perforations can outperform that of the traditional MPP in the considered case. This work proposes a general MPP theory that not only contains the classical Maa's theory for circular MPP, but also accounts for the MPP with petal-shaped perforations.

Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment.

The cell microenvironment has emerged as a key determinant of cell behavior and function in development, physiology, and pathophysiology. The extracellular matrix (ECM) within the cell microenvironment serves not only as a structural foundation for cells but also as a source of three-dimensional (3D) biochemical and biophysical cues that trigger and regulate cell behaviors. Increasing evidence suggests that the 3D character of the microenvironment is required for development of many critical cell responses observed in vivo, fueling a surge in the development of functional and biomimetic materials for engineering the 3D cell microenvironment. Progress in the design of such materials has improved control of cell behaviors in 3D and advanced the fields of tissue regeneration, in vitro tissue models, large-scale cell differentiation, immunotherapy, and gene therapy. However, the field is still in its infancy, and discoveries about the nature of cell-microenvironment interactions continue to overturn much early progress in the field. Key challenges continue to be dissecting the roles of chemistry, structure, mechanics, and electrophysiology in the cell microenvironment, and understanding and harnessing the roles of periodicity and drift in these factors. This review encapsulates where recent advances appear to leave the ever-shifting state of the art, and it highlights areas in which substantial potential and uncertainty remain.

Translation of a Coated Rigid Spherical Inclusion in an Elastic Matrix: Exact Solution, and Implications for Mechanobiology.

The displacement of relatively rigid beads within a relatively compliant, elastic matrix can be used to measure the mechanical properties of the matrix. For example, in mechanobiological studies, magnetic or reflective beads can be displaced with a known external force to estimate the matrix modulus. Although such beads are generally rigid compared to the matrix, the material surrounding the beads typically differs from the matrix in one or two ways. The first case, as is common in mechanobiological experimentation, is the situation in which the bead must be coated with materials such as protein ligands that enable adhesion to the matrix. These layers typically differ in stiffness relative to the matrix material. The second case, common for uncoated beads, is the situation in which the beads disrupt the structure of the hydrogel or polymer, leading to a region of enhanced or reduced stiffness in the neighborhood of the bead. To address both cases, we developed the first analytical solution of the problem of translation of a coated, rigid spherical inclusion displaced within an isotropic elastic matrix by a remotely applied force. The solution is applicable to cases of arbitrary coating stiffness and size of the coating. We conclude by discussing applications of the solution to mechanobiology.

Biofriendly, Stretchable, and Reusable Hydrogel Electronics as Wearable Force Sensors.

The ever-growing overlap between stretchable electronic devices and wearable healthcare applications is igniting the discovery of novel biocompatible and skin-like materials for human-friendly stretchable electronics fabrication. Amongst all potential candidates, hydrogels with excellent biocompatibility and mechanical features close to human tissues are constituting a promising troop for realizing healthcare-oriented electronic functionalities. In this work, based on biocompatible and stretchable hydrogels, a simple paradigm to prototype stretchable electronics with an embedded three-dimensional (3D) helical conductive layout is proposed. Thanks to the 3D helical structure, the hydrogel electronics present satisfactory mechanical and electrical robustness under stretch. In addition, reusability of stretchable electronics is realized with the proposed scenario benefiting from the swelling property of hydrogel. Although losing water would induce structure shrinkage of the hydrogel network and further undermine the function of hydrogel in various applications, the worn-out hydrogel electronics can be reused by simply casting it in water. Through such a rehydration procedure, the dehydrated hydrogel can absorb water from the surrounding and then the hydrogel electronics can achieve resilience in mechanical stretchability and electronic functionality. Also, the ability to reflect pressure and strain changes has revealed the hydrogel electronics to be promising for advanced wearable sensing applications.

Magnetic steering of liquid metal mobiles.

Gallium-based liquid metal has captivated exceptionally keen interest in recent years since it remains in the liquid phase at room temperature and thus conforms to the surrounding medium. Meanwhile, such morphing capability can be tuned via altering the oxide layer on the surface of the liquid metal, which further triggers enthusiasm for investigating its locomotion. In this study, we proposed a magnetic actuation scenario for steering liquid metal locomotion in an easily accessible and highly directed manner. The soft mobile composed of liquid metal performed satisfyingly in locomotion and assembly tasks in various circumstances (on a solid surface and in a water environment). Furthermore, promising applications as switches for logic circuits and carriers for cargo transfer, as well as motors for vessel cleaning were also demonstrated, revealing the versatility of such liquid metal mobiles.

In vitro diagnosis of DNA methylation biomarkers with digital PCR in breast tumors.

Liquid biopsy of cancers using DNA methylation biomarkers has received significant interest, where the quantification of multiple biomarkers is generally needed for improving the sensitivity and specificity of cancer diagnosis. However, the inefficiency of the traditional quantitative polymerase chain reaction (qPCR)-based MethyLight assay for detecting the extremely low concentration of methylated DNA fragments in body fluids limits its clinical applications. Here, we developed an ultrasensitive microwell chip digital polymerase chain reaction (dPCR)-based MethyLight assay. Using the synthesized samples, the developed MethyLight assay can achieve 103-104-fold lower limit of detection and 1-16-fold lower limit of quantification than the traditional MethyLight assay. Four hypermethylated alleles (RARß2, BRCA1, GSTP1 and RASSF1A) related to breast cancer in twenty-three clinical samples were tested using the microwell chip dPCR-based MethyLight assay. The results showed that the dPCR assay achieves ∼2 times enhancement in the cancer detection rate over the traditional quantitative PCR. Furthermore, the dPCR can detect the healthy and benign samples, which are undetectable using the traditional MethyLight assay. In multiple gene analysis, we achieved the highest detection rate of 93.3% (in the "OR" format of RARß2 and GSTP1). Lastly, the estimated cut-off values in the dPCR assay were: <1, ∼1 to 100 and >100 (copies per µL) referring to the healthy, benign and malignant breast cancers, respectively. Therefore, the developed microwell chip dPCR-based MethyLight assay could provide a powerful tool for cancer biopsy diagnosis and disease monitoring.

[The Development of Huaxi Intelligent Endoscopic Skill Training and Assessment System].

OBJECTIVE: To develop a novel objective standardized endoscopic skill training and assessment system based on artificial intelligence technology. METHODS: By designing five basic skill parts of endoscopic operation including vision location, clamping, delivering, shearing and suturing, we achieved objective standardized indexes which gained automatically with image recognition and refined perception. RESULTS: With Huaxi intelligent endoscopic skill training system, the accurate rates of vision location, clamping, delivering, shearing and suturing were 90%, 95%, 99%, 90%, and 89%, respectively. The response and performance time were 8-10 s, <1 s, <1 s, 1-3 s, and <1 s, respectively. CONCLUSION: Huaxi intelligent endoscopic skill training and assessment system has preliminarily possessed the capability to assess the endoscopic skills of surgeons objectively.

Arabidopsis Leaf Trichomes as Acoustic Antennae.

The much studied plant Arabidopsis thaliana has been reported recently to react to the sounds of caterpillars of Pieris rapae chewing on its leaves by promoting synthesis of toxins that can deter herbivory. Identifying participating receptor cells-potential "ears"-of Arabidopsis is critical to understanding and harnessing this response. Motivated in part by other recent observations that Arabidopsis trichomes (hair cells) respond to mechanical stimuli such as pressing or brushing by initiating potential signaling factors in themselves and in the neighboring skirt of cells, we analyzed the vibrational responses of Arabidopsis trichomes to test the hypothesis that trichomes can respond acoustically to vibrations associated with feeding caterpillars. We found that these trichomes have vibrational modes in the frequency range of the sounds of feeding caterpillars, encouraging further experimentation to determine whether trichomes serve as mechanical antennae.

The Arabidopsis trichome is an active mechanosensory switch.

Trichomes ('hair cells') on Arabidopsis thaliana stem and leaf surfaces provide a range of benefits arising from their shape and disposition. These include tempting herbivores to sample constitutive toxins before they reach the bulk of the tissue. We asked whether, in addition, small mechanical disturbances such as an insect can make elicit signals that might help the plant respond to herbivory. We imaged, pressed and brushed trichomes in several ways, most notably with confocal microscopy of trichomes transgenically provided with apoplastic pH reporter apo-pHusion and cytosolic Ca2+ reporter cameleon. In parallel, we modelled trichome wall mechanics with finite element analysis. The stimulated trichome focuses force on a pliant zone and the adjoining podium of the stalk. A buckling instability can further focus force on a skirt of cells surrounding the podium, eliciting oscillations of cytosolic Ca2+ and shifts in apoplastic pH. These observations represent active physiological response. Modelling establishes that the effectiveness of force focusing and buckling is due to the peculiar tapering wall structure of the trichome. Hypothetically, these active mechanosensing functions enhance toxin synthesis above constitutive levels, probably via a priming process, thus minimizing the costly accumulation of toxins in the absence of herbivore attack but assuring rapid build-up when needed.

Trichomes as a natural biophysical barrier for plants and their bioinspired applications.

Nature has inspired mankind to create novel inventions with biomimetic structures and materials, where plants provide a significant source of inspiration. Plants have evolved a range of effective appendages, among which trichomes have attracted extensive research interest due to their enormous functions. It is important to understand trichome functions and corresponding mechanisms for their bioinspired applications. In this review, we provide a comprehensive overview of the diverse functions of trichomes, with emphasis placed upon their roles as biophysical barriers that can create a complex three-dimensional (3D) network to help the plant adapt to severe environments. Moreover, we also summarize the bioinspired applications of four typical trichomes, including needle-like, hook-like, foliar-like, and antenna-like trichomes. This review offers a new perspective of interdisciplinary research on both trichome functions and their biomimetic applications.

Fountain streaming contributes to fast tip-growth through regulating the gradients of turgor pressure and concentration in pollen tubes.

Fountain streaming is a typical microfluidic pattern in plant cells, especially for cells with a high aspect ratio such as pollen tubes. Although it has been found that fountain streaming plays crucial roles in the transport of nutrients and metabolites, the positioning of organelles and the mixing of cytoplasms, its implications for the fast tip growth of pollen tubes remain a mystery. To address this, based on the observations of asiatic lily Lilium Casablanca, we developed physical models for reverse fountain streaming in pollen tubes and solved the hydrodynamics and advection-diffusion dynamics of viscous Stokes flow in the shank and apical region of pollen tubes. Theoretical and numerical results demonstrated that the gradients of turgor pressure and concentration of wall materials along the length of pollen tubes provide undamped driving force and high-efficiency materials supply, which are supposed to contribute to the fast tip-growth of pollen tubes. The sample experimental results show that the tip-growth will be abnormal when the gradients of turgor pressure change under osmotic stress induced by different concentrations of PEG-6000 (a dehydrant).

An Integrated Stochastic Model of Matrix-Stiffness-Dependent Filopodial Dynamics.

The ways that living cells regulate their behavior in response to their local mechanical environment underlie growth, development, and healing and are important to critical pathologies such as metastasis and fibrosis. Although extensive experimental evidence supports the hypothesis that this regulation is governed by the dependence of filopodial dynamics upon extracellular matrix stiffness, the pathways for this dependence are unclear. We therefore developed a model to relate filopodial focal adhesion dynamics to integrin-mediated Rho signaling kinetics. Results showed that focal adhesion maturation, i.e., focal adhesion links reinforcement and integrin clustering, dominates over filopodial dynamics. Downregulated focal adhesion maturation leads to the biphasic relationship between extracellular matrix stiffness and retrograde flow that has been observed in embryonic chick forebrain neurons, whereas upregulated maturation leads to the monotonically decreasing relationship that has been observed in mouse embryonic fibroblasts. When integrin-mediated Rho activation and stress-dependent focal adhesion maturation are combined, the model shows how filopodial dynamics endows cells with exquisite mechanosensing. Taken together, the results support the hypothesis that mechanical and structural factors combine with signaling kinetics to enable cells to probe their environments via filopodial dynamics.