The pulse of morphogenesis: actomyosin dynamics and regulation in epithelia.

Actomyosin networks are some of the most crucial force-generating components present in developing tissues. The contractile forces generated by these networks are harnessed during morphogenesis to drive various cell and tissue reshaping events. Recent studies of these processes have advanced rapidly, providing us with insights into how these networks are initiated, positioned and regulated, and how they act via individual contractile pulses and/or the formation of supracellular cables. Here, we review these studies and discuss the mechanisms that underlie the construction and turnover of such networks and structures. Furthermore, we provide an overview of how ratcheted processivity emerges from pulsed events, and how tissue-level mechanics are the coordinated output of many individual cellular behaviors.

Depth-dependent ratcheting strains of young and adult articular cartilages by experiments and predictions.

BACKGROUND: Ratcheting strain is produced due to the repeated accumulation of compressive strain in cartilage and may be a precursor to osteoarthritis. The aim of this study was to investigate the ratcheting behaviors of young and adult articular cartilages under cyclic compression by experiments and theoretical predictions. METHODS: A series of uniaxial cyclic compression tests were conducted for young and adult cartilage, and the effects of different loading conditions on their ratcheting behaviors were probed. A theoretical ratcheting model was constructed and applied to predict the ratcheting strains of young and adult cartilages with different loading conditions. RESULTS: Ratcheting strains of young and adult cartilages rapidly increased at the initial stage, followed by a slower increase in subsequent stages. The strain accumulation value and its rate for young cartilage were greater than them for adult cartilage. The ratcheting strains of the two groups of cartilage samples decreased with increasing stress rate, while they increased with increasing stress amplitude. As the stress amplitude increased, the gap between the ratcheting strains of young and adult cartilages increased gradually. The ratcheting strains of young and adult cartilages decreased along the cartilage depth from the surface to the deep layer. The ratcheting strains of different layers increased with the compressive cycle, and the difference among the three layers was noticeable. Additionally, the theoretical predictions agreed with the experimental data. CONCLUSIONS: Overall, the ratcheting behavior of articular cartilage is affected by the degree of articular cartilage maturation.

Acquisition of a socially learned tool use sequence in chimpanzees: Implications for cumulative culture.

Cumulative culture underpins humanity's enormous success as a species. Claims that other animals are incapable of cultural ratcheting are prevalent, but are founded on just a handful of empirical studies. Whether cumulative culture is unique to humans thus remains a controversial and understudied question that has far-reaching implications for our understanding of the evolution of this phenomenon. We investigated whether one of human's two closest living primate relatives, chimpanzees, are capable of a degree of cultural ratcheting by exposing captive populations to a novel juice extraction task. We found that groups (N = 3) seeded with a model trained to perform a tool modification that built upon simpler, unmodified tool use developed the seeded tool method that allowed greater juice returns than achieved by groups not exposed to a trained model (non-seeded controls; N = 3). One non-seeded group also discovered the behavioral sequence, either by coupling asocial and social learning or by repeated invention. This behavioral sequence was found to be beyond what an additional control sample of chimpanzees (N = 1 group) could discover for themselves without a competent model and lacking experience with simpler, unmodified tool behaviors. Five chimpanzees tested individually with no social information, but with experience of simple unmodified tool use, invented part, but not all, of the behavioral sequence. Our findings indicate that (i) social learning facilitated the propagation of the model-demonstrated tool modification technique, (ii) experience with simple tool behaviors may facilitate individual discovery of more complex tool manipulations, and (iii) a subset of individuals were capable of learning relatively complex behaviors either by learning asocially and socially or by repeated invention over time. That chimpanzees learn increasingly complex behaviors through social and asocial learning suggests that humans' extraordinary ability to do so was built on such prior foundations.

Visualization of two transfer RNAs trapped in transit during elongation factor G-mediated translocation.

During protein synthesis, coupled translocation of messenger RNAs (mRNA) and transfer RNAs (tRNA) through the ribosome takes place following formation of each peptide bond. The reaction is facilitated by large-scale conformational changes within the ribosomal complex and catalyzed by elongtion factor G (EF-G). Previous structural analysis of the interaction of EF-G with the ribosome used either model complexes containing no tRNA or only a single tRNA, or complexes where EF-G was directly bound to ribosomes in the posttranslocational state. Here, we present a multiparticle cryo-EM reconstruction of a translocation intermediate containing two tRNAs trapped in transit, bound in chimeric intrasubunit ap/P and pe/E hybrid states. The downstream ap/P-tRNA is contacted by domain IV of EF-G and P-site elements within the 30S subunit body, whereas the upstream pe/E-tRNA maintains tight interactions with P-site elements of the swiveled 30S head. Remarkably, a tight compaction of the tRNA pair can be seen in this state. The translocational intermediate presented here represents a previously missing link in understanding the mechanism of translocation, revealing that the ribosome uses two distinct molecular ratchets, involving both intra- and intersubunit rotational movements, to drive the synchronous movement of tRNAs and mRNA.

Remora fish suction pad attachment is enhanced by spinule friction.

The remora fishes are capable of adhering to a wide variety of natural and artificial marine substrates using a dorsal suction pad. The pad is made of serial parallel pectinated lamellae, which are homologous to the dorsal fin elements of other fishes. Small tooth-like projections of mineralized tissue from the dorsal pad lamella, known as spinules, are thought to increase the remora's resistance to slippage and thereby enhance friction to maintain attachment to a moving host. In this work, the geometry of the spinules and host topology as determined by micro-computed tomography and confocal microscope data, respectively, are combined in a friction model to estimate the spinule contribution to shear resistance. Model results are validated with natural and artificially created spinules and compared with previous remora pull-off experiments. It was found that spinule geometry plays an essential role in friction enhancement, especially at short spatial wavelengths in the host surface, and that spinule tip geometry is not correlated with lamellar position. Furthermore, comparisons with pull-off experiments suggest that spinules are primarily responsible for friction enhancement on rough host topologies such as shark skin.

Prediction of Short- to Long-Term Cyclic Deformation Behavior and Fatigue Life of Polymers.

The prediction of mechanical behavior and fatigue life is of major importance for design and for replacing costly and time-consuming tests. The proposed approach for polymers is a combination of a fatigue model and a governing constitutive model, which is formulated using the Haward-Thackray viscoplastic model (1968) and is capable of capturing large deformations. The fatigue model integrates high- and low-cycle fatigue and is based on the concept of damage evolution and a moving endurance surface in the stress space, therefore memorizing the load history without requesting vague cycle-counting approaches. The proposed approach is applicable for materials in which the fatigue development is ductile, i.e., damage during the formation of microcracks controls most of the fatigue life (up to 90%). Moreover, damage evolution shows a certain asymptote at the ultimate of the low-cycle fatigue, a second asymptote at the ultimate of the high-cycle fatigue (which is near zero), and a curvature of how rapidly the transition between the asymptotes is reached. An interesting matter is that similar to metals, many polymers satisfy these constraints. Therefore, all the model parameters for fatigue can be given in terms of the Basquin and Coffin-Manson model parameters, i.e., satisfying well-defined parameters.

Incremental Growth Analysis of a Cantilever Beam under Cyclic Thermal and Axial Loads.

Ratcheting analysis for cantilever beams subjected to the thermomechanical loads is presented using the finite element method. The cantilever beam is constrained along the vertical direction, and plane stress conditions are assumed according to the bilinear isotropic hardening model. Two points are considered to obtain areas of ratcheting by using linear extrapolation. The results and output diagrams for ratcheting with elastic-perfect plastic behavior are illustrated. It was revealed that the beam behaves elastically after the first considerable plastic strain, which is seen in two shakedown regimes. The numerical results are verified with known and analytical results in the literature. The results indicate a strong correlation between the outcomes from the cyclic ANSYS Parametric Design Language (APDL) model and Bree's analytical predictions. This consistency between the finite element analysis and the analytical solutions underscores the potential of finite element analysis as a powerful tool for addressing complex engineering challenges, offering a reliable and robust alternative to traditional analytical methods.

Use of a novel magnetically actuated compression system to study the temporal dynamics of axial and lateral strain in human osteochondral plugs.

The high water content of articular cartilage allows this biphasic tissue to withstand large compressive loads through fluid pressurization. The system presented here, termed the "MagnaSquish", provides new capabilities for quantifying the effect of rehydration on cartilage behavior during cyclic loading. An imbalanced rate of fluid exudation during load and fluid re-entry during recovery can lead to the accumulation of strain during successive loading cycles - a phenomenon known as ratcheting. Typical experimental systems for cartilage biomechanics use continuous contact between the platen and sample, which may affect tissue rehydration by compressing the top layer of cartilage and slowing fluid re-entry. To address this limitation, we developed a magnetically actuated device that provides full lift-off of the platen in between loading cycles. We investigated strain accumulation in cadaveric human osteochondral plugs during 750 loading cycles, with two dimensional profiles of the cartilage captured at 30 frames per second throughout loading and 10 min of additional free swelling recovery. Axial and lateral strain measurements were extracted from the tissue profiles using a UNet-based deep learning algorithm to circumvent manual tracing. We observed increased axial strain accumulation with shorter inter-cycle recovery, with static loading serving as the extreme case of zero recovery. The loading waveform during the 750 cycles dictated the pace of the recovery during the extended free swelling period, as shorter inter-cycle recovery led to more persistent axial strain accumulation for up to five minutes. This work showcases the importance of fluid re-entry in resisting strain accumulation during cyclical compression.

Molecular dynamics simulation on creep-ratcheting behavior of columnar nanocrystalline aluminum.

Creep-ratcheting deformation behavior of columnar nanocrystalline (NC) Al varying in grain sizes have been studied using molecular dynamics simulations at three different temperatures (300 K, 467 K, and 653 K). The underlying deformation mechanisms of columnar NC Al for two stress ratios of ratcheting are also evaluated in this study. The highest strain accumulation and rapid hysteresis loop proliferation are attained at 653 K. The dislocation density is low at 653 K in contrast to the other two deformation temperatures. The perfect dislocations support the creep-deformation process followed by Shockley partial dislocations. It is observed that the cyclic hardening phenomenon at 300 K and the cyclic softening phenomenon at 653 K dominate during creep-ratcheting loading. The specimen fails earlier at higher temperatures owing to the change in the shape of hysteresis loops. The predominant grain boundary-based deformation mechanisms of columnar NC Al specimens are grain boundary (GB) migration, GB diffusion, GB widening, GB sliding, and GBs merging for all the deformation temperatures. The variation in the extent of deformation with respect to temperatures depends on strain accumulation in the plastic region under creep-ratcheting loading.

Influence of Microalloying on the Microstructures and Properties of Spalling-Resistant Wheel Steel.

Microalloyed steels have emerged to replace conventional plain-carbon steels to achieve longer wheel life on Chinese railroads. In this work, with the aim of preventing spalling, a mechanism that consists of ratcheting and shakedown theory correlated with steel properties is systematically investigated. Mechanical and ratcheting tests were carried out for microalloyed wheel steel to which vanadium was added in the range of 0-0.15 wt.% and the results were compared with that obtained for conventional plain-carbon wheel steel. The microstructure and precipitation were characterized via microscopy. As a result, the grain size was not obviously refined, and the pearlite lamellar spacing decreased from 148 nm to 131 nm in microalloyed wheel steel. Moreover, an increase in the number of vanadium carbide precipitates was observed, which were mainly dispersed and uneven, and precipitated in the pro-eutectoid ferrite region, in contrast to the observation of lower precipitation in the pearlite. It has been found that vanadium addition can lead to an increase in yield strength by precipitation strengthening, with no reduction or increase in tensile strength, elongation or hardness. The ratcheting strain rate for microalloyed wheel steel was determined to be lower than that for plain-carbon wheel steel via asymmetrical cyclic stressing tests. An increase in the pro-eutectoid ferrite content leads to beneficial wear, which can diminish spalling and surface-initiated RCF.

Fatigue Behavior of the FGH96 Superalloy under High-Temperature Cyclic Loading.

Strain-controlled low-cycle fatigue (LCF) tests and stress-controlled creep-fatigue interaction (CFI) tests on the FGH96 superalloy were carried out at 550 °C to obtain the cyclic softening/hardening characteristics at different strain amplitudes and ratcheting strain characteristics under different hold time. The failure mechanism of the FGH96 superalloy under different loading conditions was analyzed through fracture observations. The results show that the FGH96 superalloy exhibits different cyclic softening/hardening characteristics at different strain amplitudes, and the introduction of the hold time at peak stress exacerbates the ratcheting strain of the FGH96 superalloy under asymmetric stress cycles. Fracture observations show that the magnitude of the strain amplitude, high-temperature oxidation, and the introduction of the hold time will affect the mechanical properties of the FGH96 superalloy and change its fracture mode.

Accumulation of Plastic Strain at Notch Root of Steel Specimens Undergoing Asymmetric Fatigue Cycles: Analysis and Simulation.

The present study evaluates the ratcheting response at notch roots of 1045 steel specimens experiencing uniaxial asymmetric fatigue cycles. Local stress and strain components at the notch root were analytically evaluated through the use of Neuber, Glinka, and Hoffman-Seeger (H-S) rules coupled with the Ahmadzadeh-Varvani (A-V) kinematic hardening model. Backstress promotion through coupled kinematic hardening model with the Hoffman-Seeger, Neuber, and Glinka rules was studied. Relaxation in local stresses on the notched samples as hysteresis loops moved forward with plastic strain accumulation during asymmetric loading cycles was observed. Local ratcheting results were simulated through FE analysis, where the Chaboche model was employed as the materials hardening rule. A consistent response of the ratcheting values was evidenced as predicted, and simulated results were compared with the measured ratcheting data.

Enhanced Atmospheric Water Harvesting with Sunlight-Activated Sorption Ratcheting.

The global challenge of clean water scarcity needs to be confronted with novel sustainable, climate neutral solutions, over the entire spectrum of possible clean water availability. Atmospheric moisture represents a major untapped resource that can be harvested by sorbents, enabling water production in dry inland regions where it is needed. While benefiting from the utilization of an important renewable energy source, solar-driven, sorbent-based atmospheric water harvesting systems are inseparably based on a single water harvesting cycle per day, which severely limits the daily water productivity and the competitiveness of this very promising technology. Here, we rationally design an atmospheric water harvesting strategy, using durable hydrogel sorbents, that operates with sorption "ratcheting"─a large sequence of rapid adsorption and subsequent desorption steps─activated by direct sunlight. Employing theoretical considerations, we tailor the ratcheting timescales to the inherent sorption properties of the hydrogels, optimally exploiting their natural harvesting capabilities, while maintaining the sustainable utility of the daily cycle. Amplified by the favorable sorption properties and ratcheting stability of the sorbent, this strategy demonstrates an impressive ∼80% increase in water harvesting yield over the daily cycle systems. The generic nature of the ratcheting concept shows great potential to advance the water harvesting capabilities of a range of related systems.

Stress-Controlled Creep-Fatigue of an Advanced Austenitic Stainless Steel at Elevated Temperatures.

Creep-fatigue interaction occurs in many structural components of high-temperature systems operating under cyclic and steady-state service conditions, such as in nuclear power plants, aerospace, naval, and other industrial applications. Thus, understanding micromechanisms governing high-temperature creep-fatigue behavior is essential for safety and design considerations. In this work, stress-controlled creep-fatigue tests of advanced austenitic stainless steel (Alloy 709) were performed at a 400 MPa stress range and 750 °C with tensile hold times of 0, 60, 600, 1800, and 3600 s, followed by microstructural examinations. The creep-fatigue lifetime of the Alloy 709 was found to decrease with increasing hold time until reaching a saturation level where the number of cycles to failure did not exhibit a significant decrease. Softening behavior was observed at the beginning of the test, possibly due to the recovery of entangled dislocations and de-twining. In addition, hysteresis loops showed ratcheting behavior, although the mean stress was zero during creep-fatigue cycling, which was attributed to activity of partial dislocations. Microstructural examination of the fracture surfaces showed that fatigue failure dominated at small hold times where the cracks initiated at the surface of the sample. Larger creep cracks were found for longer hold times with a lower probability of dimpled cavities, indicating the dominance of creep deformation. The results were compared with other commonly used stainless steels, and plausible reasons for the observed responses were described.

A PtdIns(3,4,5)P3 dispersal switch engages cell ratcheting at specific cell surfaces.

Force generation in epithelial tissues is often pulsatile, with actomyosin networks generating contractile forces before cyclically disassembling. This pulsed nature of cytoskeletal forces implies that there must be ratcheting mechanisms that drive processive transformations in cell shape. Previous work has shown that force generation is coordinated with endocytic remodeling; however, how ratcheting becomes engaged at specific cell surfaces remains unclear. Here, we report that PtdIns(3,4,5)P3 is a critical lipid-based cue for ratcheting engagement. The Sbf RabGEF binds to PIP3, and disruption of PIP3 reveals a dramatic switching behavior in which medial ratcheting is activated and epithelial cells begin globally constricting apical surfaces. PIP3 enrichments are developmentally regulated, with mesodermal cells having high apical PIP3 while germband cells have higher interfacial PIP3. Finally, we show that JAK/STAT signaling constitutes a second pathway that combinatorially regulates Sbf/Rab35 recruitment. Our results elucidate a complex lipid-dependent regulatory machinery that directs ratcheting engagement in epithelial tissues.

Recursive feedback between matrix dissipation and chemo-mechanical signaling drives oscillatory growth of cancer cell invadopodia.

Most extracellular matrices (ECMs) are known to be dissipative, exhibiting viscoelastic and often plastic behaviors. However, the influence of dissipation, in particular mechanical plasticity in 3D confining microenvironments, on cell motility is not clear. In this study, we develop a chemo-mechanical model for dynamics of invadopodia, the protrusive structures that cancer cells use to facilitate invasion, by considering myosin recruitment, actin polymerization, matrix deformation, and mechano-sensitive signaling pathways. We demonstrate that matrix dissipation facilitates invadopodia growth by softening ECMs over repeated cycles, during which plastic deformation accumulates via cyclic ratcheting. Our model reveals that distinct protrusion patterns, oscillatory or monotonic, emerge from the interplay of timescales for polymerization-associated extension and myosin recruitment dynamics. Our model predicts the changes in invadopodia dynamics upon inhibition of myosin, adhesions, and the Rho-Rho-associated kinase (ROCK) pathway. Altogether, our work highlights the role of matrix plasticity in invadopodia dynamics and can help design dissipative biomaterials to modulate cancer cell motility.

Ratcheting-fatigue behavior of trabecular bone under cyclic tensile-compressive loading.

This study aims to investigate the ratcheting-fatigue behaviors of trabecular bone under cyclic tension-compression, which are produced due to the accumulations of residual strain in trabecular bone. Simultaneously, the effects of different loading conditions on ratcheting behaviors of trabecular bone were probed. It is found that the gap between ratcheting strains under three stress amplitudes will gradually widen. As the stress amplitude increases, the ratcheting strain also increases. Mean stress has a significant effect on the ratcheting strain. When the mean stress is 0 MPa and 0.155 MPa, the ratcheting strain increases with the number of cycles. However, when the mean stress is -0.155 MPa, the ratcheting strain decreases as the cycle goes on. The existence of double stress peak holding time causes the creep deformation of trabecular bone, which leads to the increase of ratcheting strain. It is also noted that the ratcheting strain is greatly increased with prolongation of stress peak holding time. The digital image correlation (DIC) technique was applied to analyze the fatigue failure of trabecular bone under cyclic tension-compression. It is found that the increase of stress amplitude accelerates the damage of sample and further reduces its fatigue life. Cracks are observed in trabecular bone sample, and it is noted that the crack propagation is rapid during cyclic loading.

Long-Term Cyclic Loading Impact on the Creep Deformation Mechanism in Cohesive Materials.

Long-term cyclic loading is observed in a wide range of human activities, as well as in nature, such as in the case of ocean waves. Cyclic loading can lead to ratcheting which is defined as progressive accumulation of plastic deformation in a material. Long-term cyclic loading causes a time effect (creep), which is a secondary compression effect. In this article, we conducted 15 triaxial tests on four types of cohesive materials in undrained conditions to evaluate the damage and failure mechanism. To characterize the strain and pore pressure development, we modified the Yanbu resistance concept. On the basis of the static creep tests, we concluded that the stress paths for undrained creep behavior have to take into account the pore pressure developed during long-term cyclic loading. Pore pressure build-up and plastic strain accumulation during long-term cyclic loading are dependent on the number of loading cycles. Finally, we proposed the failure criterion, which was based on the Modified Cam-Clay constitutive model.

RhoA Mediates Epithelial Cell Shape Changes via Mechanosensitive Endocytosis.

Epithelial remodeling involves ratcheting behavior whereby periodic contractility produces transient changes in cell-cell contact lengths, which stabilize to produce lasting morphogenetic changes. Pulsatile RhoA activity is thought to underlie morphogenetic ratchets, but how RhoA governs transient changes in junction length, and how these changes are rectified to produce irreversible deformation, remains poorly understood. Here, we use optogenetics to characterize responses to pulsatile RhoA in model epithelium. Short RhoA pulses drive reversible junction contractions, while longer pulses produce irreversible junction length changes that saturate with prolonged pulse durations. Using an enhanced vertex model, we show this is explained by two effects: thresholded tension remodeling and continuous strain relaxation. Our model predicts that structuring RhoA into multiple pulses overcomes the saturation of contractility and confirms this experimentally. Junction remodeling also requires formin-mediated E-cadherin clustering and dynamin-dependent endocytosis. Thus, irreversible junction deformations are regulated by RhoA-mediated contractility, membrane trafficking, and adhesion receptor remodeling.

Use of Zipper Ratcheting Straps as a Bailout for Postoperative Cerebrospinal Fluid Leaks: Our Experience.

STUDY DESIGN: Technical note. OBJECTIVES: Management of postoperative cerebrospinal fluid (CSF) leaks is a challenge. Reexploration increases the morbidity risks. The main objective was to evaluate the outcomes of noninvasive zipper-like system (Zip surgical skin closure system, ZipLine Medical, Inc, Campbell, CA, USA) as a bailout technique for postoperative CSF leaks. METHODS: Retrospective case series. Consecutive patients with postoperative CSF leaks that occurred secondary to spinal surgeries performed between January 2017 and September 2018 were part of the study. All these patients were managed conservatively by reinforcement with zipper ratcheting straps over the sutured surgical wound. Successful clinical outcomes included cessation of CSF leaks and adequate wound healing in the postoperative period and at follow-up. RESULTS: Ten patients underwent the application of zipper ratcheting straps. The mean follow-up was 6 months (range 6 months to 1 year). In 7 cases, the dural tears were recognized postoperatively and in 3 cases, the tears were noted intraoperatively and repaired and reinforced with fibrin sealants. None of the patients developed wound soakage or subsequent CSF leak from the wound after the application of zipper ratcheting straps. CONCLUSIONS: Zipper ratcheting straps as augmentation to sewing of the wound seem to be a good alternative and bailout in treating patients with postoperative CSF leaks. The ease of its application, the ability in minimizing the complications associated with CSF leaks, and negating the need of surgical reexploration makes it a worthy option.