Adhesion Traction Research Articles

Short-range correlation of stress chains near solid-to-liquid transition in active monolayers.

Using a three-dimensional model of cell monolayers, we study the spatial organization of active stress chains as the monolayer transitions from a solid to a liquid state. The critical exponents that characterize this transition map the isotropic stress percolation onto the two-dimensional random percolation universality class, suggesting short-range stress correlations near this transition. This mapping is achieved via two distinct, independent pathways: (i) cell-cell adhesion and (ii) active traction forces. We unify our findings by linking the nature of this transition to high-stress fluctuations, distinctly linked to each pathway. The results elevate the importance of the transmission of mechanical information in dense active matter and provide a new context for understanding the non-equilibrium statistical physics of phase transition in active systems.

Reverse Mechanotransduction: Driving Chromatin Compaction to Decompaction Increases Cell Adhesion Strength and Contractility.

Mechanical extracellular signals elicit chromatin remodeling via the mechanotransduction pathway, thus determining cellular function. However, the reverse pathway is an open question: does chromatin remodeling shape cells, regulating their adhesion strength? With fluidic force microscopy, we can directly measure the adhesion strength of epithelial cells by driving chromatin compaction to decompaction with chromatin remodelers. We observe that chromatin compaction, induced by performing histone acetyltransferase inhibition or ATP depletion, leads to a reduction in nuclear volume, disrupting actin cytoskeleton and focal adhesion assembly, and ultimately decreases in cell adhesion strength and traction force. Conversely, when chromatin decompaction is drived by removing the remodelers, cells recover their original shape, adhesion strength, and traction force. During chromatin decompaction, cells use depolymerized proteins to restore focal adhesion assemblies rather than neo-synthesized cytoskeletal proteins. We conclude that chromatin remodeling shapes cells, regulating adhesion strength through a reverse mechanotransduction pathway from the nucleus to the cell surface involving RhoA activation.

Distinct platelet F-actin patterns and traction forces on von Willebrand factor versus fibrinogen

Upon vascular injury, platelets form a hemostatic plug by binding to the subendothelium and to each other. Platelet-to-matrix binding is initially mediated by von Willebrand factor (VWF) and platelet-to-platelet binding is mediated mainly by fibrinogen and VWF. After binding, the actin cytoskeleton of a platelet drives its contraction, generating traction forces that are important to the cessation of bleeding. Our understanding of the relationship between adhesive environment, F-actin morphology, and traction forces is limited. Here, we examined F-actin morphology of platelets attached to surfaces coated with fibrinogen and VWF. We identified distinct F-actin patterns induced by these protein coatings and found that these patterns were identifiable into three classifications via machine learning: solid, nodular, and hollow. We observed that traction forces for platelets were significantly higher on VWF than on fibrinogen coatings and these forces varied by F-actin pattern. In addition, we analyzed the F-actin orientation in platelets and noted that their filaments were more circumferential when on fibrinogen coatings and having a hollow F-actin pattern, while they were more radial on VWF and having a solid F-actin pattern. Finally, we noted that subcellular localization of traction forces corresponded to protein coating and F-actin pattern: VWF-bound, solid platelets had higher forces at their central region while fibrinogen-bound, hollow platelets had higher forces at their periphery. These distinct F-actin patterns on fibrinogen and VWF and their differences in F-actin orientation, force magnitude, and force localization could have implications in hemostasis, thrombus architecture, and venous versus arterial thrombosis.

Cellular segregation in cocultures is driven by differential adhesion and contractility on distinct timescales

Cellular sorting and pattern formation are crucial for many biological processes such as development, tissue regeneration, and cancer progression. Prominent physical driving forces for cellular sorting are differential adhesion and contractility. Here, we studied the segregation of epithelial cocultures containing highly contractile, ZO1/2-depleted MDCKII cells (dKD) and their wild-type (WT) counterparts using multiple quantitative, high-throughput methods to monitor their dynamical and mechanical properties. We observe a time-dependent segregation process governed mainly by differential contractility on short (<5 h) and differential adhesion on long (>5 h) timescales. The overly contractile dKD cells exert strong lateral forces on their WT neighbors, thereby apically depleting their surface area. Concomitantly, the tight junction-depleted, contractile cells exhibit weaker cell-cell adhesion and lower traction force. Drug-induced contractility reduction and partial calcium depletion delay the initial segregation but cease to change the final demixed state, rendering differential adhesion the dominant segregation force at longer timescales. This well-controlled model system shows how cell sorting is accomplished through a complex interplay between differential adhesion and contractility and can be explained largely by generic physical driving forces.

Compressive stress drives adhesion-dependent unjamming transitions in breast cancer cell migration.

Cellular unjamming is the collective fluidization of cell motion and has been linked to many biological processes, including development, wound repair, and tumor growth. In tumor growth, the uncontrolled proliferation of cancer cells in a confined space generates mechanical compressive stress. However, because multiple cellular and molecular mechanisms may be operating simultaneously, the role of compressive stress in unjamming transitions during cancer progression remains unknown. Here, we investigate which mechanism dominates in a dense, mechanically stressed monolayer. We find that long-term mechanical compression triggers cell arrest in benign epithelial cells and enhances cancer cell migration in transitions correlated with cell shape, leading us to examine the contributions of cell–cell adhesion and substrate traction in unjamming transitions. We show that cadherin-mediated cell–cell adhesion regulates differential cellular responses to compressive stress and is an important driver of unjamming in stressed monolayers. Importantly, compressive stress does not induce the epithelial–mesenchymal transition in unjammed cells. Furthermore, traction force microscopy reveals the attenuation of traction stresses in compressed cells within the bulk monolayer regardless of cell type and motility. As traction within the bulk monolayer decreases with compressive pressure, cancer cells at the leading edge of the cell layer exhibit sustained traction under compression. Together, strengthened intercellular adhesion and attenuation of traction forces within the bulk cell sheet under compression lead to fluidization of the cell layer and may impact collective cell motion in tumor development and breast cancer progression.

Regulation of cardiomyocyte adhesion and mechanosignalling through distinct nanoscale behaviour of integrin ligands mimicking healthy or fibrotic extracellular matrix.

The stiffness of the cardiovascular environment changes during ageing and in disease and contributes to disease incidence and progression. Changing collagen expression and cross-linking regulate the rigidity of the cardiac extracellular matrix (ECM). Additionally, basal lamina glycoproteins, especially laminin and fibronectin regulate cardiomyocyte adhesion formation, mechanics and mechanosignalling. Laminin is abundant in the healthy heart, but fibronectin is increasingly expressed in the fibrotic heart. ECM receptors are co-regulated with the changing ECM. Owing to differences in integrin dynamics, clustering and downstream adhesion formation this is expected to ultimately influence cardiomyocyte mechanosignalling; however, details remain elusive. Here, we sought to investigate how different cardiomyocyte integrin/ligand combinations affect adhesion formation, traction forces and mechanosignalling, using a combination of uniformly coated surfaces with defined stiffness, polydimethylsiloxane nanopillars, micropatterning and specifically designed bionanoarrays for precise ligand presentation. Thereby we found that the adhesion nanoscale organization, signalling and traction force generation of neonatal rat cardiomyocytes (which express both laminin and fibronectin binding integrins) are strongly dependent on the integrin/ligand combination. Together our data indicate that the presence of fibronectin in combination with the enhanced stiffness in fibrotic areas will strongly impact on the cardiomyocyte behaviour and influence disease progression.This article is part of the theme issue ‘The cardiomyocyte: new revelations on the interplay between architecture and function in growth, health, and disease’.

Single-molecule Force Microscopy: A Powerful Tool for Studying the Mechanical Properties of Cell Membranes

Background: Cell membrane is a physical barrier for cells, as well as an important structure with complex functions in cell activities. The cell membrane can not only receive external mechanical signal stimulation and make response (e.g. cell migration, differentiation, tumorigenesis, growth), but it can also spontaneously exert force on the environment to regulate cell activities (such as tissue repair, tumor metastasis, extracellular matrix regulation, etc.). Methods: This review provides the introduction of single-molecule force methods, as atomic force microscopy, optical tweezers, magnetic tweezers, micropipette adhesion assay, tension gauge tethers and traction force microscopy. Results: This review summarizes the principles, advantages and disadvantages of single-molecule force methods developed in recent years as well as their application in terms of force received and generated by cells. The study of cell mechanics enables us to understand the nature of mechanical signal transduction and the manifestation of the cell's own movement. Conclusion: The study of the mechanical properties of cell microenvironment leads to a gradual understanding of the important role of cell mechanics in development, physiology and pathology. Recently developed combined methods are beneficial to further study of cell mechanics. The optimization of these methods and the invention of new methods enable the continuing research on cell mechanics.

Inner Nuclear Membrane Protein, SUN1, is Required for Cytoskeletal Force Generation and Focal Adhesion Maturation.

The linker of nucleoskeleton and cytoskeleton (LINC) complex is composed of the inner nuclear membrane-spanning SUN proteins and the outer nuclear membrane-spanning nesprin proteins. The LINC complex physically connects the nucleus and plasma membrane via the actin cytoskeleton to perform diverse functions including mechanotransduction from the extracellular environment to the nucleus. Mammalian somatic cells express two principal SUN proteins, namely SUN1 and SUN2. We have previously reported that SUN1, but not SUN2, is essential for directional cell migration; however, the underlying mechanism remains elusive. Because the balance between adhesive force and traction force is critical for cell migration, in the present study, we focused on focal adhesions (FAs) and the actin cytoskeleton. We observed that siRNA-mediated SUN1 depletion did not affect the recruitment of integrin β1, one of the ubiquitously expressed focal adhesion molecules, to the plasma membrane. Consistently, SUN1-depleted cells normally adhered to extracellular matrix proteins, including collagen, fibronectin, laminin, and vitronectin. In contrast, SUN1 depletion reduced the activation of integrin β1. Strikingly, the depletion of SUN1 interfered with the incorporation of vinculin into the focal adhesions, whereas no significant differences in the expression of vinculin were observed between wild-type and SUN1-depleted cells. In addition, SUN1 depletion suppressed the recruitment of zyxin to nascent focal adhesions. These data indicate that SUN1 is involved in the maturation of focal adhesions. Moreover, disruption of the SUN1-containing LINC complex abrogates the actin cytoskeleton and generation of intracellular traction force, despite the presence of SUN2. Thus, a physical link between the nucleus and cytoskeleton through SUN1 is required for the proper organization of actin, thereby suppressing the incorporation of vinculin and zyxin into focal adhesions and the activation of integrin β1, both of which are dependent on traction force. This study provides insights into a previously unappreciated signaling pathway from the nucleus to the cytoskeleton, which is in the opposite direction to the well-known mechanotransduction pathways from the extracellular matrix to the nucleus.

Imaging dynamic three-dimensional traction stresses.

Traction stress between contact objects is ubiquitous and crucial for various physical, biological, and engineering processes such as momentum transfer, tactile perception, and mechanical reliability. Newly developed techniques including electronic skin or traction force microscopy enable traction stress measurement. However, measuring the three-dimensional distribution during a dynamic process remains challenging. Here, we demonstrated a method based on stereo vision to measure three-dimensional traction stress with high spatial and temporal resolution. It showed the ability to image the two-stage adhesion failure of bionic microarrays and display the contribution of elastic resistance and adhesive traction to rolling friction at different contact regions. It also revealed the distributed sucking and sealing effect of the concavity pedal waves that propelled a snail crawling in the horizontal, vertical, and upside-down directions. We expected that the method would advance the understanding of various interfacial phenomena and greatly benefit related applications across physics, biology, and robotics.

The cellular and molecular mechanisms of cerebrovascular regeneration and repair

<p indent=0mm>Stroke is a severe acute cerebrovascular disease that can cause a number of neuronal deaths and brain edema. The treatment of ischemic stroke mainly includes hyperacute vascular recanalization and later pro-angiogenesis therapy. At present, the promotion of angiogenesis is mainly through the combined application of vascular growth factors and guidance molecules, and the transplantation of endothelial progenitor cells to promote vascular regeneration and repair. Pericytes can promote angiogenesis and rebuild brain-blood-barrier. Activated platelets shed microparticles, which contain a variety of growth factors central to angiogenesis and neurogenesis during brain vascular regeneration. The newly discovered meningeal lymphatic vessels can invade the injured parenchyma to resolve edema and act as “growing tracks” to guide the growth of nascent blood vessels. These functions of pericytes, platelets, and the meningeal lymphatics suggest their potential as novel pro-angiogenic targets for ischemic stroke. In addition to ischemic stroke, microbleeds resulting from ruptures in microvessels are also a very extensive chronic cerebrovascular disease. After cerebral microbleeds, microglia can mediate the repair of brain vascular rupture through direct physical adhesion and mechanical traction. Here, we review the cellular and molecular mechanisms in cerebral vascular regeneration and repair. In addition, we provide our perspectives for future mechanistic studies and treatment strategies for neurovascular diseases.

Реабілітація хворих з переломами дистального метаепіфіза променевої кістки

Переломи дистального метаепіфіза променевої кістки (ПДМЕПК, переломи променя в типовому місці) зустрічаються досить часто, особливо у людей похилого віку. Незадовільні результати лікування у пацієнтів віком понад 70 років відмічаються у 44 % випадків. Робота присвячена поліпшенню результатів лікування хворих із переломами дистального метаепіфіза променевої кістки. Реабілітаційне лікування включало мультимодальне знеболювання, диференційовано і обґрунтовано застосовану медикаментозну терапію, щадну репозицію із застосуванням запропонованого пристрою, ранню кінезитерапію, масаж і фізіотерапію. Функціональні результати реабілітації хворих із переломами ДМЕПК за шкалою DASH свідчили про її високу ефективність.

Cell adhesion strength and tractions are mechano-diagnostic features of cellular invasiveness.

The adhesion of cells to substrates occurs via integrin clustering and binding to the actin cytoskeleton. Oncogenes modify anchorage-dependent mechanisms in cells during cancer progression. Fluid shear devices provide a label-free way to characterize cell-substrate interactions and heterogeneities in cell populations. We quantified the critical adhesion strengths of MCF-7, MDAMB-231, A549, HPL1D, HeLa, and NIH3T3 cells using a custom fluid shear device. The detachment response was sigmoidal for each cell type. A549 and MDAMB-231 cells had significantly lower critical adhesion strengths (τ50) than their non-invasive counterparts, HPL1D and MCF-7. Detachment dynamics inversely correlated with cell invasion potentials. A theoretical model, based on τ50 values and the distribution of cell areas on substrates, provided good fits to results from de-adhesion experiments. Quantification of cell tractions, using the Reg-FTTC method on 10 kPa polyacrylamide gels, showed highest values for invasive, MDAMB-231 and A549, cells compared to non-invasive cells. Immunofluorescence studies show differences in vinculin distributions; non-invasive cells have distinct vinculin puncta, whereas invasive cells have more dispersed distributions. The cytoskeleton in non-invasive cells was devoid of well-developed stress fibers, and had thicker cortical actin bundles in the boundary. Fluorescence intensity of actin was significantly lower in invasive cells as compared to non invasive cells. These correlations in adhesion strengths and traction stresses with cell invasiveness may be useful in cancer diagnostics and other pathologies featuring mis-regulation in adhesion.

Integrin-based mechanosensing through conformational deformation

Conversion of integrins from low to high affinity states, termed activation, is important in biological processes, including immunity, hemostasis, angiogenesis, and embryonic development. Integrin activation is regulated by large-scale conformational transitions from closed, low affinity states to open, high affinity states. Although it has been suggested that substrate stiffness shifts the conformational equilibrium of integrin and governs its unbinding, here, we address the role of integrin conformational activation in cellular mechanosensing. Comparison of wild-type versus activating mutants of integrin αVβ3 show that activating mutants shift cell spreading, focal adhesion kinase activation, traction stress, and force on talin toward high stiffness values at lower stiffness. Although all activated integrin mutants showed equivalent binding affinity for soluble ligands, the β3 S243E mutant showed the strongest shift in mechanical responses. To understand this behavior, we used coarse-grained computational models derived from molecular level information. The models predicted that wild-type integrin αVβ3 displaces under force and that activating mutations shift the required force toward lower values, with S243E showing the strongest effect. Cellular stiffness sensing thus correlates with computed effects of force on integrin conformation. Together, these data identify a role for force-induced integrin conformational deformation in cellular mechanosensing.

Роль интраокулярной гидродинамики в индуцировании отслойки задней гиалоидной мембраны (предварительное сообщение)

At present, it is believed that the detachment of the vitreous body occurs due to the contraction and liquefaction of the vitreous body, while the exit of the liquid part of the vitreum into the retrovitreal space passes passively through the formed prepapillary opening, after which the vitreous body collapses, however, more precise mechanisms have not been described. Purpose. Substantiate a hypothesis of influence of intravitreal hydrodynamics in inducing detachment of the posterior hyaloid membrane based on the analysis of OCT data. Material and methods. An OCT study was performed in 30 patients with initial detachment of the posterior hyaloid membrane (PHM) with macular adhesion, macular traction, and macular hole. The features of the location of the PHM in the region of the macula, foveola and the place of attachment of the PHM to the optic nerve were studied. Results and discussion. As a result of the analysis of OCT images, it was found that with macular holes, macular adhesion and macular traction, a closed space is formed between the posterior hyaloid membrane and the retina (subbursal space) in the form of a dome, which indirectly indicates an increase in pressure within this space. In 28 patients, the zone of dissection or thinning of the PHM was found parapapillary, through which the intraocular fluid is likely to be injected into the subbursal space. Conclusions: This study suggests the leading role of intravitreal hydrodynamics and the formation of an area of increased pressure in the subbursal space in the induction of the detachment of the PHM, the pathogenesis of vitreomacular adhesion, vitreomacular traction and macular hole. The topic requires more detailed study. Key words: posterior hyaloid membrane, OCT, vitreous body, macular hole.

Challenges and progress in the understanding and modelling of the wheel–rail creep forces

This paper surveys advances in the understanding and modelling of wheel–rail creep forces. The main focus is placed on tribological aspects, for which significant progress was made in the past two decades. We emphasise the role played by the surface conditions, i.e. the presence of liquid and solid layers, surface roughness, and near-surface plastic deformation. As these surface conditions may change over time, transient changes may be obtained in the creep force characteristic. This brings feedback into the picture, with consequences and opportunities for optimised adhesion recovery, traction control, and braking systems.

Self-Compliant Track-Type Wall-Climbing Robot for Variable Curvature Facade

The paper presents a wall-climbing robot featuring self-compliance for variable curvature fa&#x00E7;ades. The high payload and maneuverability make it highly potential in heavy-duty operation of industrial applications. The robot consists of two traction modules and one link module. Each traction module is equipped with magnetic adhesion and crawler traction submodules. The two traction modules are connected by the link module with 4 degrees of freedom (DoF) of passive compliance. Variable curvature fa&#x00E7;ade self-compliance is achieved by the passive compliant link module, which results in the attitude change decoupling of the two traction modules. The attitude can be adjusted under the effect of magnetic adhesion force to comply with the curvature variations. High payloads are achieved by the large contact area between the crawler and the surface. Omni-directional high maneuverability is enabled by the speed difference between the motors of two traction modules. The robot can maneuver in any direction on the surface with a minimum radius of 1 m and carry 36 kg payload on vertical surfaces.

Optimization design and experimental analysis of bionic viscosity reduction of chisel type energy saving subsoiling shovel

In order to solve the problems of adhesion to soil and high resistance in traditional subsoiling shovel operation, a bionic energy-saving subsoiling shovel with bionic viscosity reducing and resistance reducing chisel is designed based on the polygon geometry structure of pangolin scales. In this paper, the bionic modeling analysis of chisel type energy-saving subsoiling shovel is carried out by using 3D modeling software. According to the simulation analysis data, we optimize the key structural parameters, and try to produce the bionic energy-saving deep scarifier with reducing viscosity and resistance. In order to study the performance of the chisel type energy-saving subsoiling shovel, L9 (34) orthogonal test was carried out in the field with the number of bionic surfaces, coating materials and forward speed as the experimental factors, and the adhesion soil amount and traction resistance as the test indexes. The results show that the order of influence of each factor on the index is the number of subsoiling shovel bionic surface, coating material and advancing speed; the optimal horizontal combination is that the number of bionic surfaces of subsoiling shovel is 10, the coating material is UHMWPE, and the advancing speed is 6km/h.

Tensile force transmitted through LFA-1 bonds mechanoregulate neutrophil inflammatory response.

Recruitment of leukocytes to sites of acute inflammation is guided by spatial and temporal cues that ensure appropriate cell numbers infiltrate the tissue at precise locations to protect it from infection and initiate repair. On inflamed endothelium, neutrophil rolling via selectins elicits cytosolic calcium release from endoplasmic reticulum (ER)-stores that are synergistic with chemokine signaling to activate formation of high affinity (HA) LFA-1 bonds to ICAM-1, which is necessary to anchor cells against the drag force of blood flow. Bond tension on LFA-1 within the area of adhesive contact with endothelium elicits calcium entry through calcium release-activated calcium channel protein 1 (Orai-1) membrane channels that in turn activate neutrophil shape change and migration. We hypothesized that mechanotransduction via LFA-1 is mediated by assembly of a cytosolic molecular complex consisting of Kindlin-3, receptor for activated C kinase 1 (RACK1), and Orai1. Initiation of Ca2+ flux at sites of adhesive contact required a threshold level of shear stress and increased with the magnitude of bond tension transduced across as few as 200 HA LFA-1. A sequential mechanism triggered by force acting on LFA-1/Kindlin-3 precipitated dissociation of RACK1, which formed a concentration gradient above LFA-1 bond clusters. This directed translocation of ER proximal to Orai1, where binding of inositol 1,4,5-triphosphate receptor type 1 and activation via stromal interaction molecule 1 elicited Ca flux and subsequent neutrophil shape change and motility. We conclude that neutrophils sense adhesive traction on LFA-1 bonds on a submicron scale to direct calcium influx, thereby ensuring sufficient shear stress of blood flow is present to trigger cell arrest and initiate transmigration at precise regions of vascular inflammation.

The self-organized differentiation from MSCs into SMCs with manipulated micro/Nano two-scale arrays on TiO2 surfaces for biomimetic construction of vascular endothelial substratum.

The endothelialization on biomaterial surface has been seen as an important strategy to solve the clinic problems with the cardiovascular implant device. However, the continuous and large surfaces such as artificial heart or artificial cardiac valve cannot maintain the structural and functional stability of the endothelium without the supply of substratum structures. Herein, we combined the micro/nano technology of material surface engineering and the tissue engineering technology to construct the biomimetic vascular endothelial substratum for high quality and complete endothelialization through inducing self-organized differentiation from MSCs to SMCs, controlling their self-aggregation structure and further manipulating micro-tissue on the surface. In the present work, the micro/nano two-scale features of surface were manipulated by preparing the micro arrays of TiO2 nanotubes on titanium surface. The responses of MSCs to these surfaces revealed that the MSCs could be highly regulated and then their self-organized differentiation to SMCs could be induced and improved based on anchoring of the adhesion complex protein and traction of F-actin adjusted by the micro/nano features of the surfaces. Besides, SMCs' self-aggregation structure could also be adjusted effectively by manipulating micro/nano features on two-scale surfaces, and three types of tissue-like structures could be achieved for the further use in formation and surface manipulation of micro-tissue and biomimetic construction of vascular endothelial substratum.

Effect of Surface Roughness on Adhesive Instabilities for the Elastic Layer

If an incompressible elastic layer bonded to a rigid plane is placed close to a second rigid plane, adhesive interactions between the surfaces can cause elastic instabilities. These lead to spatially non-uniform traction and gap distributions which exhibit a regular pattern with a characteristic wavenumber. However, real surfaces are never completely plane. In this paper, we consider the influence of surface roughness on the instability, with particular reference to the force-displacement relation. With random roughness profiles, the traction distributions are always spatially irregular, so the onset of instability is more difficult to define. One approach is to monitor the amplitude of the power spectrum of the distribution near the characteristic wavenumber. Since surface roughness generally reduces the mean adhesive traction, we might expect it to exert a stabilizing effect. Numerical results confirm this for moderate to large RMS amplitudes, but show that low RMS roughness can actually trigger the instability in ranges where the uniform layer would be stable. The resulting traction-displacement relation is then found to be approximately linear with a slope close to that at the point where the uniform solution loses stability.