Helical twist controls the thickness of F-actin bundles

In the presence of condensing agents such as nonadsorbing polymer, multivalent counter ions, and specific bundling proteins, chiral biopolymers typically form bundles with a finite thickness, rather than phase-separating into a polymer-rich phase. Although short-range repulsive interactions or geometrical frustrations are thought to force the equilibrium bundle size to be limited, the precise mechanism is yet to be resolved. The importance of the tight control of biopolymer bundle size is illustrated by the ubiquitous cytoskeletal actin filament bundles that are crucial for the proper functioning of cells. Using an in vitro model system, we show that size control relies on a mismatch between the helical structure of individual actin filaments and the geometric packing constraints within bundles. Small rigid actin-binding proteins change the twist of filamentous actin (F-actin) in a concentration-dependent manner, resulting in small, well defined bundle thickness up to approximately 20 filaments, comparable to those found in filopodia. Other F-actin cross-linking proteins can subsequently link these small, well organized bundles into larger structures of several hundred filaments, comparable to those found in, for example, Drosophila bristles. The energetic tradeoff between filament twisting and cross-linker binding within a bundle is suggested as a fundamental mechanism by which cells can precisely adjust bundle size and strength.     

Topological defects produce kinks in biopolymer filament bundles

Bundles of stiff filaments are ubiquitous in the living world, found both in the cytoskeleton and in the extracellular medium. These bundles are typically held together by smaller cross-linking molecules. We demonstrate, analytically, numerically, and experimentally, that such bundles can be kinked, that is, have localized regions of high curvature that are long-lived metastable states. We propose three possible mechanisms of kink stabilization: a difference in trapped length of the filament segments between two cross-links, a dislocation where the endpoint of a filament occurs within the bundle, and the braiding of the filaments in the bundle. At a high concentration of cross-links, the last two effects lead to the topologically protected kinked states. Finally, we explore, numerically and analytically, the transition of the metastable kinked state to the stable straight bundle.

Semiflexible biopolymer filaments, that is, stiff filaments whose thermal persistence length is comparable to their length, form most of the structural elements within cells and in the extracellular matrix surrounding them in tissues. Common intracellular examples include the F-actin and intermediate filaments forming the cytoskeleton, while the extracellular matrix making up most tissues is composed of other stiff filamentous structures, such as collagen and elastin fibers. The three-dimensional (3D) structure of these fiber networks is typically fixed by a variety of specific cross-linking proteins. On a smaller scale, these filaments often share a similar structural motif—they form bundles of nearly aligned filaments, which are often densely cross-linked along their contours.While bundles might be regarded merely as new and thicker (thus stiffer) filaments, this analysis is inadequate in detail. For instance, bundle bending mechanics can dramatically differ from those of a simple filament because, by having extra degrees of freedom associated with sliding one constituent filament relative to another within the bundle, the bundle acquires a length-dependent effective bending modulus (1, 2). These internal degrees of freedom also suggest that a nearly parallel group of filaments, when quenched into a bundle by the addition of cross-linking agents, may end up in one of many metastable states in which cross-linking traps a defect, that is, a long-lived structure distinct from the elastic ground state of straight, parallel, and densely cross-linked filaments. We focus on these defected, metastable states and their effect on the low-energy configurations of the bundle. Specifically, we show that there are three types of defects, two of which correspond to topological defects in the bundle’s unstressed state—braids and dislocations. These and a third form of trapped length (loops) are all long-lived structures due to cross-linking.As a result of these structural defects within the bundle, the elastic reference state is no longer straight, even though straight filament configurations are individually the lowest-energy state of the constituent filaments. Bundles containing these defects can minimize their elastic energy by taking on localized bends, which we call kinks. The presence of kinks allows one to relate the micron-scale contour of kinked filament bundles to their nanoscale structure, specifically, the presence of length-trapping defects. We show that the combination of theory and simulation of defected bundles can account for the distribution of kinks we observe in experiment. Over long times, defects slowly anneal in bundles. This slow relaxation of the bundle’s structure can be understood in terms of the diffusion and interaction of the defects on it. Specifically, defects leave the bundle either through diffusion off the bundle’s ends or by the annihilation of defects within it.Not only do defected bundles explain the apparent kinks in collagen fibers, but the presence of defects also has implications for the collective elastic response of the bundle. In particular, we show that kinks are more bending compliant than undefected lengths of a bundle. As a result, we hypothesize that the collective mechanics of a network of defected bundles depends on the number and position of these quenched defects, which act like soft hinges in a 3D network of bundles that behave more like stiff beams.Topological defects are well known in condensed matter, including, for example, disclinations in nematic liquid crystals and dislocations in crystalline solids (3–5). Defect motion plays a dominant role in the plastic deformation of many solids. Dislocations and disclinations are topological defects; their removal requires a system-sized reorganization of interatomic bonds. The defects in filament bundles share this feature. They cannot be removed without breaking a number of cross-links proportional to the bundle length (we consider the filaments to always be unbreakable). This feature ensures that the defects are long lived on the scale of the thermal undulations of the bundles themselves.In our observations of collagen networks, we find kinked bundles, whose contour we quantify by measuring their local curvature using light microscopy. Due to their connection to the network, we cannot be certain that these kinks are not in some way related to elastic stress in the network. To address this question, we used large-scale Brownian dynamics simulations to study kinking in quenched filaments with force- and torque-free boundary conditions, finding that quenched defects produce a statistical distribution of kinks similar to those observed in the experiment. Using the simulations, we are also able to measure the reduction of the bundle’s local bending modulus at the location of the defects and observe the motion of the defects along the bundle. Finally, we present theoretical calculations using a simple model of semiflexible filaments that demonstrate the relationship between defects and kinks in the bundle. Moreover, we analytically determine (and test via simulation) the time evolution of the number of defects in a bundle as they slowly anneal through defect–defect annihilation or by diffusion off the ends.We first report our observations from light microscopy of kinks in collagen bundles and compare these kinks with those from numerical simulations. We then present a general discussion of the three types of defects and demonstrate that the minimum energy state of the defected bundle can be kinked. We explore defect dynamics, estimating the lifetime of a kink and the number of kinks in a bundle as a function of time, which we compare to simulation. To properly describe interaction of braiding type defects, we use the theory of the braid group; some relevant background is provided in SI Appendix, section 3.     

扩散张量成像及扩散张量纤维束成像在颅脑肿瘤诊断中的应用价值

目的探讨磁共振扩散张量成像(DTI)及纤维束成像(DTT)在星形细胞瘤、脑膜瘤与转移瘤肿瘤实质区的应用价值,通过对表观扩散系数(ADC)及各向异性分数(FA)的测量分析,观察脑白质与纤维束的关系,为临床提供有价值的信息。方法对32例经病理证实的脑肿瘤患者,其中不同级别星形细胞瘤12例、良性脑膜瘤10例、转移瘤10例,分别测量肿瘤实质区与对应区正常脑组织的平均ADC值和FA值,分析其ADC值和FA值的差异并观察3种脑肿瘤对白质纤维束的影响。结果星形细胞瘤、脑膜瘤或转移瘤患者组内肿瘤实质区与对侧正常脑组织FA值差异有统计学意义(P<0.05),星形细胞瘤、脑膜瘤、转移瘤患者肿瘤实质区的FA值分别为0.07±0.03、0.14±0.05、0.16±0.07,P<0.05。星形细胞瘤及转移瘤患者肿瘤实质区ADC值较对侧正常脑组织高(P<0.05);脑膜瘤患者肿瘤实质区ADC值与对侧正常部位无显著性差异(P>0.05);星形细胞瘤、脑膜瘤和转移瘤患者肿瘤实质区ADC值差异有统计学意义(P<0.05)。在DTT图中星形细胞瘤和转移瘤多数表现为纤维束部分中断、受压、偏移或变形移位;脑膜瘤纤维束呈现为稀疏,移位。结论测量肿瘤实质区ADC值及FA值可用于鉴别脑内和脑外的肿瘤,如星形细胞瘤与脑膜瘤的鉴别或转移瘤与脑膜瘤的鉴别,其中ADC值有显著的鉴别意义;DTT可清晰显示正常白质纤维束和肿瘤的解剖关系,有利于术前方案的制定。     

Direct measurement of force generation by actin filament polymerization using an optical trap

Actin filament polymerization generates force for protrusion of the leading edge in motile cells. In protrusive structures, multiple actin filaments are arranged in cross-linked webs (as in lamellipodia or pseudopodia) or parallel bundles (as in filopodia). We have used an optical trap to directly measure the forces generated by elongation of a few parallel-growing actin filaments brought into apposition with a rigid barrier, mimicking the geometry of filopodial protrusion. We find that the growth of approximately eight actin parallel-growing filaments can be stalled by relatively small applied load forces on the order of 1 pN, consistent with the theoretical load required to stall the elongation of a single filament under our conditions. Indeed, large length fluctuations during the stall phase indicate that only the longest actin filament in the bundle is in contact with the barrier at any given time. These results suggest that force generation by small actin bundles is limited by a dynamic instability of single actin filaments, and therefore living cells must use actin-associated factors to suppress this instability to generate substantial forces by elongation of parallel bundles of actin filaments.     

Non-euclidean geometry of twisted filament bundle packing

Densely packed and twisted assemblies of filaments are crucial structural motifs in macroscopic materials (cables, ropes, and textiles) as well as synthetic and biological nanomaterials (fibrous proteins). We study the unique and nontrivial packing geometry of this universal material design from two perspectives. First, we show that the problem of twisted bundle packing can be mapped exactly onto the problem of disc packing on a curved surface, the geometry of which has a positive, spherical curvature close to the center of rotation and approaches the intrinsically flat geometry of a cylinder far from the bundle center. From this mapping, we find the packing of any twisted bundle is geometrically frustrated, as it makes the sixfold geometry of filament close packing impossible at the core of the fiber. This geometrical equivalence leads to a spectrum of close-packed fiber geometries, whose low symmetry (five-, four-, three-, and twofold) reflect non-euclidean packing constraints at the bundle core. Second, we explore the ground-state structure of twisted filament assemblies formed under the influence of adhesive interactions by a computational model. Here, we find that the underlying non-euclidean geometry of twisted fiber packing disrupts the regular lattice packing of filaments above a critical radius, proportional to the helical pitch. Above this critical radius, the ground-state packing includes the presence of between one and six excess fivefold disclinations in the cross-sectional order.     

Mechanical Properties of Aramid/Carbon Hybrid Fiber-Reinforced Concrete

In this study, aramid fiber (Kevlar^® 29 fiber) and carbon fiber were added into concrete in a hybrid manner to enhance the static and impact mechanical properties. The coupling agent presence on the surface of carbon fibers was spotted in Scanning Electron Microscope (SEM) and energy-dispersive X-ray spectroscopy (EDS) graphs. The carbon fiber with a coupling agent affected the mechanical strength of the reinforced concrete. At 1% fiber/cement weight percentage, the hybrid fiber-reinforced concrete (HFRC) prepared using Kevlar fiber and carbon fiber of 12 and 24 mm in length under different mix proportions was investigated to determine the maximum mechanical strengths. From the test results, the mechanical strength of the HFRC attained better performance than that of the concrete with only Kevlar or carbon fibers. Foremost, the mix proportion of Kevlar/carbon fiber (50–50%) significantly improved the compressive, flexural, and splitting tensile strengths. Under different impact energies, the impact resistance of the HFRC specimen was much higher than that of the benchmark specimen, and the damage of the HFRC specimens was examined with an optical microscope to identify slippage or rupture failure of the fiber in concrete.     

Coupling a sensory hair-cell bundle to cyber clones enhances nonlinear amplification

The vertebrate ear benefits from nonlinear mechanical amplification to operate over a vast range of sound intensities. The amplificatory process is thought to emerge from active force production by sensory hair cells. The mechano-sensory hair bundle that protrudes from the apical surface of each hair cell can oscillate spontaneously and function as a frequency-selective, nonlinear amplifier. Intrinsic fluctuations, however, jostle the response of a single hair bundle to weak stimuli and seriously limit amplification. Most hair bundles are mechanically coupled by overlying gelatinous structures. Here, we assayed the effects of mechanical coupling on the hair-bundle amplifier by combining dynamic force clamp of a hair bundle from the bullfrog’s saccule with real-time stochastic simulations of hair-bundle mechanics. This setup couples the hair bundle to two virtual hair bundles, called cyber clones, and mimics a situation in which the hair bundle is elastically linked to two neighbors with similar characteristics. We found that coupling increased the coherence of spontaneous hair-bundle oscillations. By effectively reducing noise, the synergic interplay between the hair bundle and its cyber clones also enhanced amplification of sinusoidal stimuli. All observed effects of coupling were in quantitative agreement with simulations. We argue that the auditory amplifier relies on hair-bundle cooperation to overcome intrinsic noise limitations and achieve high sensitivity and sharp frequency selectivity.     

Dual conduction in a Mahaim fiber

The case of an 8-year-old girl with incessant nonsustained left bundle branch block-like tachycardia refractory to antiarrhythmic drug therapy is reported. Electrophysiologic study revealed the presence of a right-sided accessory atriofascicular pathway. Episodes of nonsustained tachycardia were found to be based upon a dual response in AV conduction over the Mahaim fiber to one P wave. No reentrant tachycardia could be induced. The arrhythmia was cured by catheter ablation targeting a Mahaim potential at the right lateral tricuspid annulus. The findings can be explained by longitudinal dissociation in a single Mahaim fiber, a fiber distally diverging into two fibers with different conduction times, or (less likely) two closely located Mahaim fibers with different conduction times.     

Microtubules and microfilaments during cell spreading and colony formation in PK 15 epithelial cells.

We have studied the distribution of microtubules and microfilaments during the cell spreading and subsequent colony formation in PK 15 pig kidney epithelial cells using indirect immunofluorescence. During the cell spreading on a solid substratum, microtubules grew out from the region around the nucleus, and a collar of microfilament bundles formed around the cell periphery. Although virtually all well-spread cells showed a complex microtubular network, distinctly different patterns of stress fibers were observed. In small colonies, the most commonly observed pattern was a ring of microfilament bundles that appeared to be in register between adjacent cells and encircled the entire colony in a fashion similar to that seen in single cells. In large colonies (more than 50 cells), approximately 60% of the cells displayed clearly stained microfilament bundles, either at the cell periphery or throughout their cytoplasm, whereas in the remaining 40%, no microfilament bundles were observed and only the outline of the cells was delineated by interaction with anti-actin. Such "negative" cells were seen in groups alongside "positive" cells (i.e., cells possessing extensive stress fiber networks) within the same colony. Independent of their stress fiber phenotype, all cells maintained a flattened shape and an extensive network of microtubules. We suggest that dense microfilament bundles are not a uniform feature of well-spread PI 15 cells in culture and that a loss of microfilament bundle occurs in some cells.     

Monte Carlo simulation of equilibrium globular protein folding: alpha-helical bundles with long loops.

To help elucidate the general rules of globular protein folding, computer simulations of the conformational transition in model proteins having the left-handed, four-helix bundle motif in which the helices are joined by one or two long loops, as in apoferritin and somatotropin, respectively, have been undertaken. In the context of simple tetrahedral lattice protein models, these unique native helix bundle motifs can be obtained by a set of interactions similar to those found in previous simulations of the folding of four-member alpha-helical bundles with tight bends and beta-barrel proteins including the Greek key motif. The essential features sufficient to produce the four-helix bundle motif with long loops are as follows: (i) a general pattern of hydrophobic and hydrophilic type residues which differentiate the interior from the exterior of the molecule; (ii) the existence of hydrophilic regions in the amino acid sequence that, on the basis of short-range interactions, are indifferent to loop formation but that interact favorably with all the exterior residues of the helix bundle. Thus, these simulations indicate that, to reproduce all varieties of the left-handed four-helix bundle motif, site-specific interactions are not required.     

A computer model of normal conduction in the human atria

Although considerable progress has been made in understanding the process of wavefront propagation and arrhythmogenesis in human atria, technical concerns and issues of patient safety have limited experimental investigations. The present work describes a finite volume-based computer model of human atrial activation and current flow to complement these studies. Unlike previous representations, the model is three-dimensional, incorporating both the left and right atria and the major muscle bundles of the atria, including the crista terminalis, pectinate muscles, limbus of the fossa ovalis, and Bachmann's bundle. The bundles are represented as anisotropic structures with fiber directions aligned with the bundle axes. Conductivities are assigned to the model to give realistic local conduction velocities within the bundles and bulk tissue. Results from simulations demonstrate the role of the bundles in a normal sinus rhythm and also reveal the patterns of activation in the septum, where experimental mapping has been extremely challenging. To validate the model, the simulated normal activation sequence and conduction velocities at various locations are compared with experimental observations and data. The model is also used to investigate paced activation, and a mechanism of the relative lengthening of left versus right stimulation is presented. Owing to both the realistic geometry and the bundle structures, the model can be used for further analysis of the normal activation sequence and to examine abnormal conduction, including flutter. The full text of this article is available at http://www.circresaha.org.     

Experimental Research on Mechanical Properties and Compression Constitutive Relationship of PVA Fiber-Reinforced Coral Concrete

In this paper, the mechanical properties of coral concrete with different strength and different polyvinyl alcohol (PVA) fiber content under compression were experimentally investigated. The results show that adding an appropriate amount of PVA fiber could obtain satisfactory mechanical properties of coral concrete. The stress–strain constitutive relationship of plain and PVA fiber-reinforced coral concrete was investigated by prism uniaxial compression test. The results shown that the incorporation of PVA fiber had a significant effect on limiting the development of concrete internal cracks, and effectively improved the mechanical properties of coral concrete after cracking, especially the toughness. Different constitutive models from previous research were used to describe the axial compressive stress–strain relationship of plain and PVA fiber-reinforced coral concrete, and a piecewise function model was finally selected which is most consistent with the experimental curve and its characteristic points. In addition, determination of critical parameters for the selected constitutive model was proposed, and experimental validations confirmed its accuracy.     

Evaluation of Hybrid Melamine and Steel Fiber Reinforced Geopolymers Composites

This study investigated the influence of the steel and melamine fibers hybridization on the flexural and compressive strength of a fly ash-based geopolymer. The applied reinforcement reduced the geopolymer brittleness. Currently, there are several types of polymer fibers available on the market. However, the authors did not come across information on the use of melamine fibers in geopolymer composites. Two systems of reinforcement for the composites were investigated in this work. Reinforcement with a single type of fiber and a hybrid system, i.e., two types of fibers. Both systems strengthened the base material. The research results showed the addition of melamine fibers as well as steel fibers increased the compressive and flexural strength in comparison to the plain matrix. In the case of a hybrid system, the achieved results showed a synergistic effect of the introduced fibers, which provided better strength results in relation to composites reinforced with a single type of fiber in the same amount by weight.     

Experimental and Numerical Investigation into Failure Modes of Tension Angle Members Connected by One Leg

This paper presents the results of experimental and numerical tests on angle members connected by one leg with a single row of bolts. This study was designed to determine which failure mode governs the resistance of such joints: net section rupture or block tearing rupture. Experimental tests were insufficient to completely identify the failure modes, and it was necessary to conduct numerical simulations. Finite element analysis of steel element resistance based on rupture required advanced material modelling, taking into account ductile initiation and propagation of fractures. This was realised using the Gurson–Tvergaard–Needleman porous material model, which allows for analysis of the joint across the full scope of its behaviour, from unloaded state to failure. Through experimental testing and numerical simulations, both failure mechanisms (net section and block tearing) were examined, and an approach to identify the failure mode was proposed. The obtained results provided experimental and numerical evidence to validate the strength function used in design standards. Finally, the obtained results of the load capacity were compared with the design procedures given in the Eurocode 3′s current and 2021 proposed editions.     

Seismic Performance of Steel Fiber Reinforced High–Strength Concrete Beam–Column Joints

In high–strength concrete, the reinforcement concentration will cause some problems in the beam–column joints (BCJs) due to a large amount of transverse reinforcement. Hence, the main object of this paper is to prevent the reinforcement concentration and reduce the amount of transverse reinforcement in the BCJs through the ideal usage of steel fibers and reinforced high–strength concrete. Pseudo–static tests on seven specimens were carried out to investigate and evaluate the seismic performance of beam–column joints in steel fiber reinforced high–strength concrete (SFRHC). Test variables were steel fiber volume ratio, concrete strength, the stirrup ratio in the core area, and an axial compression ratio of the column end. During the test, the hysteresis curves and failure mode were recorded. The seismic indicators, such as energy dissipation, ductility, strength, and stiffness degradation, were determined. The experimental results indicated that the failure modes of SFRHC beam–column joints mainly included the core area failure and the beam end bending failure. With the increase in stirrup ratio, volume ratio of steel fiber, and axial compression ratio in the core area, both the ductility and energy consumption of beam–column joints increased, while the opposite was true for concrete strength.     

Mechanical and Durability Properties of Latex-Modified Hybrid Fiber-Reinforced Roller-Compacted Rapid-Set Cement Concrete for Pavement Repair

This study evaluated the mechanical properties and durability performance of latex-modified hybrid fiber-reinforced roller-compacted rapid-set cement concrete (LMHFRCRSC) for emergency repair of concrete pavement. Experimental parameters included the blend ratio of the hybrid fiber, which comprised natural jute fiber (0–0.2 vol.%) and structural synthetic fiber (0–2 vol.%). The mechanical performance of LMHFRCRSC of various blend ratios was evaluated in terms of compressive, flexural, and splitting tensile strength. Durability assessment included chlorine ion penetration and abrasion resistance measurements. Compressive and flexural strength values of 21 and 3.5 MPa, respectively, were the set targets after 4 h of curing; a compressive strength of 35 MPa, a flexural strength of 4.5 MPa, a splitting tensile strength of 4.2 MPa, and chloride ion penetration of 2000 C or less were required after 28 days of curing. Our test results confirmed that all mix proportions satisfied the target values, regardless of the blend ratio of the hybrid fiber. Specifically, the mechanical performance of the concrete improved as the blend ratio of the structural synthetic fiber increased. With regard to durability, a greater amount of jute fiber, a hydrophilic fiber, enhanced the concrete’s durability. Additionally, incorporating jute fiber of 0.6 kg/m³ provided excellent chlorine ion penetration resistance. The optimal blend ratio for the hybrid fiber was natural jute fiber at 0.6 kg/m³ and structural synthetic fiber at 13.65 kg/m³ (mix: J0.6 + P13.65); with this mix proportion, a chloride ion penetration amount of 1000 C or less and maximum mechanical performance were achieved.     

Numerical Study of the Optimum Fiber Content of Sealing Grease Using Discrete Element Method

A sealing grease plays a crucial role in the sealing of shield tails. Its pumpability and pressure sealing resistant sealing performance are greatly affected by the fiber content. In this study, discrete element method models were used to simulate the pressure-resistant tests of sealing grease in order to investigate the influence of viscosity grade and fiber’s aspect ratio on the optimum fiber content of sealing grease. Meanwhile, the rationality of the optimum fiber number determined based on the sealing performance was verified with the unbalanced force and fiber area proportion obtained in the simulation, of which the variation curves with the increasing fiber number were practically identical. The simulation results elucidated that the viscosity of grease had little effect on the optimum fiber content for sealing grease. However, the increase in viscosity can improve the sealing effect, and increasing the fiber’s aspect ratio can reduce the fiber number to reach a specific seal state. Based on the analysis of the total number of fiber spheres for the models with different fiber’s respect ratios, it can be concluded that the sealing grease sample made of the same fiber material and quality can reach the same seal state and seal effect, independent on fiber’s aspect ratio.     

Improved Shear Strength Prediction Model of Steel Fiber Reinforced Concrete Beams by Adopting Gene Expression Programming

In this study, an artificial intelligence tool called gene expression programming (GEP) has been successfully applied to develop an empirical model that can predict the shear strength of steel fiber reinforced concrete beams. The proposed genetic model incorporates all the influencing parameters such as the geometric properties of the beam, the concrete compressive strength, the shear span-to-depth ratio, and the mechanical and material properties of steel fiber. Existing empirical models ignore the tensile strength of steel fibers, which exercise a strong influence on the crack propagation of concrete matrix, thereby affecting the beam shear strength. To overcome this limitation, an improved and robust empirical model is proposed herein that incorporates the fiber tensile strength along with the other influencing factors. For this purpose, an extensive experimental database subjected to four-point loading is constructed comprising results of 488 tests drawn from the literature. The data are divided based on different shapes (hooked or straight fiber) and the tensile strength of steel fiber. The empirical model is developed using this experimental database and statistically compared with previously established empirical equations. This comparison indicates that the proposed model shows significant improvement in predicting the shear strength of steel fiber reinforced concrete beams, thus substantiating the important role of fiber tensile strength.