Formations of force network and softening of amorphous elastic materials from a coarsen-grained particle model.

Amorphous materials, such as granular substances, glasses, emulsions, foams, and cells, play significant roles in various aspects of daily life, serving as building materials, plastics, food products, and agricultural items. Understanding the mechanical response of these materials to external forces is crucial for comprehending their deformation, toughness, and stiffness. Despite the recognition of the formation of force networks within amorphous materials, the mechanisms behind their formation and their impact on macroscopic physical properties remain elusive. In this study, we employ a coarse-grained particle model to investigate the mechanical response, wherein local physical properties are integrated into the softness of the particles. Our findings reveal the emergence of a chain-like force distribution, which correlates with the planar distribution of softness and heterogeneous density variations. Additionally, we observe that the amorphous material undergoes softening due to the heterogeneous distribution of softness, a phenomenon explicable through a simple theoretical framework. Moreover, we demonstrate that the ambiguity regarding the size ratio of the blob to the force network can be adjusted by the amplitude of planar fluctuations in softness, underscoring the robustness of the coarse-grained particle model.

Role of tubulin C-terminal tail on mechanical properties of microtubule.

Tubulin C-terminal tail (CTT) is a disordered segment extended from each tubulin monomer of αß tubulin heterodimers, the building blocks of microtubules. The tubulin CTT contributes to the cellular function of microtubules such as intracellular transportation by regulating their interaction with other proteins and cell shape regulation by controlling microtubule polymerization dynamics. Although the mechanical integrity of microtubules is crucial for their functions, the role of tubulin CTT on microtubule mechanical properties has remained elusive. In this work, we investigate the role of tubulin CTTs in regulating the mechanical properties of microtubules by estimating the persistence lengths and investigating the buckling behavior of microtubules with and without CTT. We find that microtubules with intact CTTs exhibit twice the rigidity of microtubules lacking tubulin CTTs. Our study will widen the scope of altering microtubule mechanical properties for its application in nano bio-devices and lead to novel therapeutic approaches for neurodegenerative diseases with altered microtubule properties.

How a Soft Rod Wraps around a Rotating Cylinder.

The unique characteristics of helical coils are utilized in nature, manufacturing processes, and daily life. These coils are also pivotal in the development of soft machines, such as artificial muscles and soft grippers. The stability of these helical coils is generally dependent on the mechanical properties of the rods and geometry of the supporting objects. In this Letter, the shapes formed by a flexible, heavy rod wrapping around a slowly rotating rigid cylinder are investigated through a combination of experimental and theoretical approaches. Three distinct morphologies-tight coiling, helical wrapping, and no wrapping-are identified experimentally. These findings are rationalized by numerical simulations and a geometrically nonlinear Kirchhoff rod theory. Despite the frictional contact present, the local shape of the rod is explained by the interplay between bending elasticity, gravity, and the geometry of the system. Our Letter provides a comprehensive physical understanding of the ordered morphology of soft threads and rods. Implications of this understanding are significant for a wide range of phenomena, from the recently discovered wrapping motility mode of bacterial flagella to the design of an octopus-inspired soft gripper.

Scraping of foam on a substrate.

HYPOTHESIS: Foam is not only an industrially important form of matter, but also one of soft jammed system such as colloidal suspensions and emulsion suspensions. Since foams are composed of gas bubbles and liquid, it is expected that the coupling of bubbles and liquid strongly affects rheology of foams, which is different from simple liquids. To reveal this coupling effect and considering the importance of foam applications, we studied the scraping of foam by a rigid plate on a substrate. EXPERIMENT: We mainly used 5.0 wt% solution of ionic surfactant TTAB (tetradecyltrimethylammonium bromide). We systematically investigate the scraping behaviors by the rigid plate as a function of scraping velocity, gap height, confinement length, amount of foam and wettability of the substrate. FINDINGS: The results show that there are three distinguishable scraping patterns: homogeneous scraping, no scraping, and slendered scraping. These behaviors are clearly different from those of simple liquid systems. Of these, the upper limit of homogeneous scraping could be explained theoretically by the competition between dewetting and shear, which is not previously discussed. Furthermore, the theory is applicable to the scraping of other soft jammed systems such as colloidal and emulsion suspensions.

Filamentous crystal growth in organic liquids and selection of crystal morphology.

Filamentous crystals such as whisker crystals are often seen not only in metallic liquids, but also in organic liquids and solutions. They are interesting as reinforce materials. However, it remains challenging to induce filamentous crystals due to an incomplete understanding of the mechanisms behind their formation. In this paper, we investigate filamentous crystal growth in viscous organic liquids. It is found that filamentous crystals grow via an extraordinary dynamical path, where the molecules locally evaporate to bubbles and then redeposite to the tip of growing crystalline filaments. We also succeeded in controlling whether filamentous or faceted crystal growth is selected by inducing or suppressing the bubbles.

Pinch-off from a foam droplet in a Hele-Shaw cell.

Placing some foam on a vertical surface is a ubiquitous situation, for example, such as in shaving and wall cleaning in daily life, and in egg-laying or making foam nests for some animals or insects in nature. In such a situation, one may prefer that the foam remains in the initial position. Moreover, losing solution via liquid pinch-off from the bottom of the foam is undesirable. To address the pinching off condition and mechanism, we conducted a model experiment: we confined an amount of foam in a Hele-Shaw cell. Two sliding down modes, both with and without liquid pinch-off, were observed under gravity. We fabricated morphology phase diagrams, and theoretically clarified the onset of liquid pinch-off from a foamy droplet.

Origin of nonlinear force distributions in a composite system.

Composite materials have been actively developed in recent years because they are highly functional such as lightweight, high yield strength, and superior load response. In spite of importance of the composite materials, mechanisms of the mechanical responses of composites have been unrevealed. Here, in order to understand the mechanical responses of composites, we investigated the origin and nature of the force distribution in heterogeneous materials using a soft particle model. We arranged particles with different softness in a lamellar structure and then we applied homogeneous pressure to the top surface of the system. It is found that the density in each region differently changes and then the density difference induces a nonlinear force distribution. In addition, it is found that the attractive interaction suppresses the density difference and then the force distribution is close to the theoretical prediction. Those findings may lead material designs for functional composite materials.

Dynamics and mechanism of liquid film collapse in a foam.

Foams have unique properties that distinguish them from ordinary liquids and gases, and are ubiquitously observed in nature, both in biological systems and industrial products. Foams are known to eventually collapse over time; given their wide-range industrial application, understanding how bubbles in a foam collapse is an important aspect for product longevity and tailoring physical properties. Previously, it was shown that droplets are emitted during the collective bubble collapse, however the mechanism of the droplet emission in a foam is not yet clearly understood. It is directly related to the stability of the foam, thus we quantitatively investigate collapse dynamics in liquid films in a foam, and identify some unique features. When one film breaks, we see that the oscillation of the vertical Plateau border to which it is connected induces anomalous liquid transport from the edge of the border to the center. Once a crack appears near the border and a collapse front is formed, we find that the curvature of the front reverses as it migrates, followed by the emergence and emission of droplets. We elucidate the origins of this behavior and discuss the stability of foams, establishing how the characteristic time scales of the process relate to each other.

Towards combinatorial mixing devices without any pumps by open-capillary channels: fundamentals and applications.

In chemistry, biology, medical sciences and pharmaceutical industries, many reactions have to be checked by transporting and mixing expensive liquids. For such purposes, microfluidics systems consisting of closed channels with external pumps have been useful. However, the usage has been limited because of high fabrication cost and need for a fixed setup. Here, we show that open-capillary channels, which can be fabricated outside a clean room on durable substrates and are washable and reusable, are considerably promising for micro-devices that function without pumps, as a result of detailed studies on the imbibition of open micro-channels. We find that the statics and dynamics of the imbibition follow simple scaling laws in a wide and practical range; although a precursor film obeying a universal dynamics appears in the vertical imbibition, it disappears in the horizontal mode to make the design of complex micro-channel geometry feasible. We fabricate micro open-channel devices without any pumps to express the green fluorescent protein (GFP) by transporting highly viscous solutions and to accomplish simultaneous chemical reactions for the Bromothymol blue (BTB) solution. We envision that open-capillary devices will become a simple and low-cost option to achieve microfluidic devices that are usable in small clinics and field studies.

Capillary rise on legs of a small animal and on artificially textured surfaces mimicking them.

The wharf roach Ligia exotica is a small animal that lives by the sea and absorbs water from the sea through its legs by virtue of a remarkable array of small blades of micron scale. We find that the imbibition dynamics on the legs is rather complex on a microscopic scale, but on a macroscopic scale the imbibition length seems to simply scale linearly with elapsed time. This unusual dynamics of imbibition, which usually slows down with time, is advantageous for long-distance water transport and results from repetition of unit dynamics. Inspired by the remarkable features, we study artificially textured surfaces mimicking the structure on the legs of the animal. Unlike the case of the wharf roach, the linear dynamics were not reproduced on the artificial surfaces, which may result from more subtle features on the real legs that are not faithfully reflected on the artificial surfaces. Instead, the nonlinear dynamics revealed that hybrid structures on the artificial surfaces speed up the water transport compared with non-hybrid ones. In addition, the dynamics on the artificial surfaces turn out to be well described by a composite theory developed here, with the theory giving useful guiding principles for designing hybrid textured surfaces for rapid imbibition and elucidating physical advantages of the microscopic design on the legs.

Astrocytes as antigen-presenting cells: expression of IL-12/IL-23.

Interleukin-12 (IL-12, p70) a heterodimeric cytokine of p40 and p35 subunits, important for Th1-type immune responses, has been attributed a prominent role in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Recently, the related heterodimeric cytokine, IL-23, composed of the same p40 subunit as IL-12 and a unique p19 subunit, was shown to be involved in Th1 responses and EAE. We investigated whether astrocytes and microglia, CNS cells with antigen-presenting cell (APC) function can present antigen to myelin basic protein (MBP)-reactive T cells, and whether this presentation is blocked with antibodies against IL-12/IL-23p40. Interferon (IFN)-gamma-treated APC induced proliferation of MBP-reactive T cells. Anti-IL-12/IL-23p40 antibodies blocked this proliferation. These results support and extend our previous observation that astrocytes and microglia produce IL-12/IL-23p40. Moreover, we show that stimulated astrocytes and microglia produce biologically active IL-12p70. Because IL-12 and IL-23 share p40, we wanted to determine whether astrocytes also express IL-12p35 and IL-23p19, as microglia were already shown to express them. Astrocytes expressed IL-12p35 mRNA constitutively, and IL-23 p19 after stimulation. Thus, astrocytes, under inflammatory conditions, express all subunits of IL-12/IL-23. Their ability to present antigen to encephalitogenic T cells can be blocked by neutralizing anti-IL-12/IL-23p40 antibodies.

Photodegradation products of propranolol: the structures and pharmacological studies.

Recently, single-dose drug packaging systems, allowing the administration of multiple drugs in a single pill, have become popular for the convenience of the patient. The quality of drugs and an accurate measurement of their photostabilities within this system, however, have not been carefully addressed. Drugs that are unstable in light should be carefully handled to protect their potency and ensure their safety. Propranolol (1), a beta-adrenergic receptor antagonist, is widely used for angina pectoris, arrhythmia, and hypertension. Due to its naphthalene skeleton, this drug may be both light unstable and a photosensitizing agent. In this study, we isolated three photodegraded products of propranolol (1): 1-naphthol (2), N-acetylpropranolol (3), and N-formylpropranolol (4). The structures of these compounds were determined by spectroscopic methods and chemical syntheses. We also examined the acute toxicities of these substances in mice and their binding to beta-adrenergic receptors using rat cerebellum cortex membranes. Although the photoproducts isolated in this study did not exhibit any acute toxicity or significant binding to beta-adrenergic receptors, these results serve as a warning to single-dose packaging systems, as propranolol (1) must be handled carefully to protect the compound from light-induced degradation.

Chronic expression of monocyte chemoattractant protein-1 in the central nervous system causes delayed encephalopathy and impaired microglial function in mice.

Increased central nervous system (CNS) levels of monocyte chemoattractant protein 1 [CC chemokine ligand 2 (CCL2) in the systematic nomenclature] have been reported in chronic neurological diseases such as human immunodeficiency virus type 1-associated dementia, amyotrophic lateral sclerosis, and multiple sclerosis. However, a pathogenic role for CCL2 has not been confirmed, and there is no established model for the effects of chronic CCL2 expression on resident and recruited CNS cells. We report that aged (>6 months) transgenic (tg) mice expressing CCL2 under the control of the human glial fibrillary acidic protein promoter (huGFAP-CCL2hi tg+ mice) manifested encephalopathy with mild perivascular leukocyte infiltration, impaired blood brain barrier function, and increased CD45-immunoreactive microglia, which had morphologic features of activation. huGFAP-CCL2hi tg+ mice lacking CC chemokine receptor 2 (CCR2) were normal, showing that chemokine action via CCR2 was required. Studies of cortical slice preparations using video confocal microscopy showed that microglia in the CNS of huGFAP-CCL2hi tg+ mice were defective in expressing amoeboid morphology. Treatment with mutant CCL2 peptides, a receptor antagonist and an obligate monomer, also suppressed morphological transformation in this assay, indicating a critical role for CCL2 in microglial activation and suggesting that chronic CCL2 exposure desensitized CCR2 on microglia, which in the CNS of huGFAP-CCL2hi tg+ mice, did not up-regulate cell-surface expression of major histocompatibility complex class II, CD11b, CD11c, or CD40, in contrast to recruited perivascular macrophages that expressed enhanced levels of these markers. These results indicate that huGFAP-CCL2hi tg+ mice provide a useful model to study how chronic CNS expression of CCL2 alters microglial function and CNS physiology.

Pertussis toxin-induced reversible encephalopathy dependent on monocyte chemoattractant protein-1 overexpression in mice.

In this report we describe pertussis toxin-induced reversible encephalopathy dependent on monocyte chemoattractant protein-1 (MCP-1) overexpression (PREMO), a novel animal model that exhibits features of human encephalopathic complications of inflammatory disorders such as viral meningoencephalitis and Lyme neuroborreliosis as well as the mild toxic encephalopathy that commonly precedes relapses of multiple sclerosis (MS). Overexpression of the mouse MCP-1 gene product (classically termed JE) in astrocytes, the major physiological CNS cellular source of MCP-1, failed to induce neurological impairment. Unexpectedly, transgenic (tg) mice overexpressing MCP-1 at a high level (MCP-1(hi)) manifested transient, severe encephalopathy with high mortality after injections of pertussis toxin (PTx) plus complete Freund's adjuvant (CFA). Surviving mice showed markedly improved function and did not relapse during a prolonged period of observation. Tg mice that expressed lower levels of MCP-1 were affected minimally after CFA/PTx injections, and tg expression of other chemokines failed to elicit this disorder. The disorder was significantly milder in mice lacking T-cells, which therefore play a deleterious role in this encephalopathic process. Disruption of CC chemokine receptor 2 (CCR2) abolished both CNS inflammation and encephalopathy, identifying CCR2 as a relevant receptor for this disorder. Proinflammatory and type 1 cytokines including TNF-alpha, IL-1beta, IFN-gamma, IL-2, RANTES, and IP-10 were elevated in CNS tissues from mice with PREMO. These studies characterize a novel model of reversible inflammatory encephalopathy that is dependent on both genetic and environmental factors.

Chemokines and chemokine receptors in inflammatory demyelinating neuropathies: a central role for IP-10.

Inflammatory cell recruitment is an important step in the pathogenesis of autoimmune demyelinating diseases of the PNS. Chemokines might play a critical role in promoting leucocyte entry into the nervous system during immune-mediated inflammation. Here, we report the expression pattern of the chemokine receptors CCR-1, CCR-2, CCR-4, CCR-5 and CXCR-3 in sural nerve biopsies obtained from patients with classical Guillain-Barré syndrome (acute inflammatory demyelinating polyradiculoneuropathy), chronic inflammatory demyelinating polyradiculoneuropathy and various non-inflammatory neuropathies. A consistent chemokine receptor expression pattern was immunohistochemically detected in inflammatory demyelinating neuropathies and quantitation of labelled mononuclear cells revealed significantly elevated cell counts compared with controls. CCR-1 and CCR-5 were primarily expressed by endoneurial macrophages, whereas CCR-2, CCR-4 and CXCR-3 could be localized to invading T lymphocytes. Quantitative analysis revealed that CXCR-3 was expressed at highest numbers by infiltrating T cells compared with the other receptors. Thus, expression and distribution of CXCR-3 suggest a specific role of this receptor in chemokine-mediated lymphocyte traffic into the inflamed PNS tissue. Therefore, we further analysed the expression of its ligands interferon-gamma-inducible protein of 10 kDa (IP-10) and monokine induced by interferon-gamma (Mig). Significantly increased levels of IP-10 could be measured in the CSF of patients with inflammatory neuropathies, whereas no differences were observable for Mig. In situ hybridization for IP-10 mRNA mirrored the distribution of the cognate receptor within the inflamed PNS, and delineated endothelial cells as the primary cellular source of IP-10. Our results imply a pathogenic role for specific chemokine receptors and IP-10 in the genesis of inflammatory demyelinating neuropathies.