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#mechanical

20 posts7 participants0 posts today
Rxiv mechanobio

📰 "Rheological transition driven by matrix makes cancer spheroids resilient under confinement"
doi.org/doi:10.26508/lsa.20240
pubmed.ncbi.nlm.nih.gov/401479
#Mechanical #Matrix #Ecm

Life Science Alliance · Rheological transition driven by matrix makes cancer spheroids resilient under confinementCancer metastasis through confining peritoneal microenvironments is mediated by spheroids: clusters of disseminated cells. Ovarian cancer spheroids are frequently cavitated; such blastuloid morphologies possess an outer ECM coat. We investigated the effects of these spheroidal morphological traits on their mechanical integrity. Atomic force microscopy showed blastuloids were elastic compared with their prefiguring lumenless moruloid counterparts. Moruloids flowed through microfluidic setups mimicking peritoneal confinement, exhibited asymmetric cell flows during entry, were frequently disintegrated, and showed an incomplete and slow shape recovery upon exit. In contrast, blastuloids exhibited size-uncorrelated transit kinetics, rapid and efficient shape recovery upon exit, symmetric cell flows, and lesser disintegration. Blastuloid ECM debridement phenocopied moruloid traits including lumen loss and greater disintegration. Multiscale computer simulations predicted that higher intercellular adhesion and dynamical lumen make blastuloids resilient. Blastuloids showed higher E-cadherin expression, and their ECM removal decreased membrane E-cadherin localization. E-cadherin knockdown also decreased lumen formation and increased spheroid disintegration. Thus, the spheroidal ECM drives its transition from a labile viscoplastic to a resilient elastic phenotype, facilitating their survival within spatially constrained peritoneal flows. The raw data for all experiments and simulations will be made available upon reasonable request.
Rxiv mechanobio

📰 "Unified Mechanical Erosion Model for Multi-phase Mass Flows"
arxiv.org/abs/2209.10880 #Physics.Flu-Dyn #Physics.Geo-Ph #Mechanical #Matrix

arXiv logo
arXiv.orgUnified Mechanical Erosion Model for Multi-phase Mass FlowsErosion poses a great challenge in multi-phase mass flows as it drastically changes flow behavior and deposition pattern by dramatically increasing their masses, adversely affecting population and civil structures. There exists no mechanically-explained, unified multi-phase erosion model. We constitute a novel, unified and comprehensive mechanical erosion rates for solid and fluid phases and demonstrate their richness and urgency. This is achieved by seminally introducing interacting stresses across erosion-interface. Shear resistances from the bed against shear stresses from the landslide are based on consistent physical principles including frictional, collisional and viscous stresses. Proposed multi-phase interactive shear structures are mechanically superior and dynamically flexible. Total erosion rate is the sum of solid and fluid erosion rates which are mechanically extensive and compact. Erosion rates consistently take solid and fluid fractions from the bed and customarily supply to solid and fluid components in the flow. This overcomes severe limitations inherited by existing models. For the first time, we physically correctly construct composite, intricate erosion velocities of particle and fluid from the bed and architect the complete net momentum productions that include all interactions between solids and fluids in the landslide and bed. We invent stress correction, erosive-shear-velocity, super-erosion-drift and erosion-matrix characterizing erosion processes. By embedding well constrained extensive erosion velocities, unified erosion rates and net momentum productions including erosion-induced inertia into mass and momentum balances, we develop a novel, mechanically-explained, comprehensive multi-phase model for erosive mass flows. The new model offers great opportunities for practitioners in solving technical, engineering problems related to erosive multi-phase mass flows.
Rxiv mechanobio

📰 "Soft matter mechanics of immune cell aggregates"
arxiv.org/abs/2503.21402 #Physics.Bio-Ph #Mechanical #Mechanics #Cell

arXiv logo
arXiv.orgSoft matter mechanics of immune cell aggregatesT-cells are a crucial subset of white blood cells that play a central role in the immune system. When T-cells bind antigens, it leads to cell activation and the induction of an immune response. If T-cells are activated by antigens in vivo or artificially in vitro, they form multicellular aggregates. The mechanical properties of such clusters provide valuable information on different T-cell activation pathways. Furthermore, the aggregate mechanics capture how T-cells are affected by mechanical forces and interact within larger conglomerates, such as lymph nodes and tumours. However, an understanding of collective T-cell adhesion and mechanics following cell activation is currently lacking. Probing the mechanics of fragile and microscopically small living samples is experimentally challenging. Here, the micropipette force sensor technique was used to stretch T-cell aggregates and directly measure their Young's modulus and ultimate tensile strength. A mechanistic model was developed to correlate how the stiffness of the mesoscale multicellular aggregate emerges from the mechanical response of the individual microscopic cells within the cluster. We show how the aggregate elasticity is affected by different activators and relate this to different activation pathways in the cells. Our soft matter mechanics study of multicellular T-cell aggregates contributes to our understanding of the biology behind immune cell activation.
Rxiv mechanobio

📰 "Extending the range of sizes of monodisperse core-shell hydrogel capsules from composite jet breakup by combined electrical and mechanical actuation"
arxiv.org/abs/2503.21333 #Physics.Flu-Dyn #Mechanical #Cell

arXiv logo
arXiv.orgExtending the range of sizes of monodisperse core-shell hydrogel capsules from composite jet breakup by combined electrical and mechanical actuationThe production of monodisperse particles or droplets is a longstanding issue across various fields, from aerosol science to inkjet printing. In bioengineering, submillimeter cell laden hydrogel capsules have proven valuable for developing in vitro tissue models. A common practical approach for producing such droplets relies on the Plateau Rayleigh instability to break up a liquid compound jet in air. However, while the droplet size is closely linked to nozzle dimensions, achieving high monodispersity suitable for quantitative biological assays remains challenging due to coalescence events associated with the beads on a string morphology of viscoelastic jets. Here, a microfluidic strategy is introduced, combining electrical and mechanical actuation to enhance control and versatility over jet breakup. By fine tuning the excitation frequency to select specific modes and applying an electric potential to regulate coalescence, a phase diagram is established, enabling the generation of monodisperse droplets over a broad size range. Notably, a previously hidden effect of the electric field on jet behavior is uncovered and quantitatively characterized. Finally, after crosslinking the compound droplets, capsules with a hydrogel envelope and a core composed of a cell suspension are formed in conditions compatible with cell proliferation, which lay the groundwork for quantitative high precision biological assays.
Rxiv mechanobio

📰 "Regulation of plasma membrane tension through hydrostatic pressure and actin protrusion forces"
biorxiv.org/content/10.1101/20 #Extracellular #Mechanical #Actin

bioRxiv · Regulation of plasma membrane tension through hydrostatic pressure and actin protrusion forcesThe plasma membrane and its associated proteins form a critical signaling hub, mediating communication between the extracellular environment and the intracellular space. Previous research suggests that both membrane trafficking and signaling activity are influenced by mechanical tension in the plasma membrane. Despite its importance, the mechanisms by which cells regulate membrane tension remain poorly understood. Using the optical tension sensor FliptR and AFM-assisted tether force measurements, we investigate plasma membrane tension regulation in mitotic cells by measuring tension changes following cytoskeletal and cell shape perturbations. Our findings show that in both assays, reported tensions are critically influenced by the cytoskeleton, however, with partially deviating trends highlighting the conceptual differences between bare and apparent membrane tension. By integrating experimental data with theoretical modeling, we demonstrate that the actin cytoskeleton regulates bare membrane tension through two distinct mechanisms: (i) modulation of intracellular hydrostatic pressure and (ii) adjustment of polymerization forces in actin-rich finger-like protrusions. ### Competing Interest Statement The authors have declared no competing interest.
Rxiv mechanobio

📰 "Empirical Hyper Element Integration Method (EHEIM) with Unified Integration Criteria for Efficient Hyper Reduced FE$^2$ Simulations"
arxiv.org/abs/2503.19483 #Physics.Comp-Ph #Mechanical #Math.Na #Cs.Na #Ecm

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arXiv.orgEmpirical Hyper Element Integration Method (EHEIM) with Unified Integration Criteria for Efficient Hyper Reduced FE$^2$ SimulationsNumerical homogenization for mechanical multiscale modeling by means of the finite element method (FEM) is an elegant way of obtaining structure-property relations, if the behavior of the constituents of the lower scale is well understood. However, the computational costs of this so-called FE$^2$ method are so high that reduction methods are essential. While the construction of a reduced basis for the microscopic nodal displacements using proper orthogonal decomposition (POD) has become a standard technique, the reduction of the computational effort for the projected nodal forces, the so-called hyper reduction, is an additional challenge, for which different strategies have been proposed in the literature. The empirical cubature method (ECM), which has been proven to be very robust, implemented the conservation of the total volume is used as a constraint in the resulting optimization problem, while energy-based criteria have been proposed in other contributions. The present contribution presents a unified integration criteria concept, involving the aforementioned criteria, among others. These criteria are used both with a Gauss point-based as well as with an element-based hyper reduction scheme, the latter retaining full compatibility with the common modular finite element framework. The methods are combined with a previously proposed clustered training strategy and a monolithic solver. Numerical examples empirically demonstrate that the additional criteria improve the accuracy for a given number of modes. Vice verse, less modes and thus lower computational costs are required to reach a given level of accuracy.
Rxiv mechanobio

📰 "Theory of multiscale epithelial mechanics under stretch: from active gels to vertex models"
biorxiv.org/content/10.1101/20 #Cytoskeletal #Mechanical #Mechanics

bioRxiv · Theory of multiscale epithelial mechanics under stretch: from active gels to vertex modelsEpithelial monolayers perform a variety of mechanical functions, which include maintaining a cohesive barrier or developing 3D shapes, while undergoing stretches over a wide range of magnitudes and loading rates. To perform these functions, they rely on a hierarchical organization, which spans molecules, cytoskeletal networks, adhesion complexes and junctional networks up to the tissue scale. While the molecular understanding and ability to manipulate cytoskeletal components within cells is rapidly increasing, how these components integrate to control tissue mechanics is far less understood, partly due to the disconnect between theoretical models of sub-cellular dynamics and those at a tissue scale. To fill this gap, here we propose a formalism bridging active-gel models of the actomyosin cortex and 3D vertex-like models at a tissue scale. We show that this unified framework recapitulates a number of seemingly disconnected epithelial time-dependent phenomenologies, including stress relaxation following stretch/unstretch maneuvers, active flattening after buckling, or nonreciprocal and non-affine pulsatile contractions. We further analyze tissue dynamics probed by a novel experimental setup operating in a pressure-controlled ensemble. Overall, the proposed framework systematically connects sub-cellular cortical dynamics and tissue mechanics, and ties a variety of epithelial phenomenologies to a common sub-cellular origin. ### Competing Interest Statement The authors have declared no competing interest.
Rxiv mechanobio

📰 "Prostate cancer associated fibroblasts have distinct morphomechanical features that are associated with patient outcome"
biorxiv.org/content/10.1101/20 #Mechanical #Cell

bioRxiv · Prostate cancer associated fibroblasts have distinct morphomechanical features that are associated with patient outcomeTumour development and progression reshape the physical properties of the surrounding tumour microenvironment (TME) including its biomechanical traits. This is driven by a prominent cell type in the TME, cancer associated fibroblasts (CAFs), which increases tissue stiffness via extracellular matrix deposition and remodelling. Currently, it is unclear whether there are also physical changes to CAFs at the cellular level and, if so, how they relate to patient outcome. Here we show that CAFs have distinct morphological and biomechanical features from normal fibroblasts. We examined matched, patient-derived CAFs and non-malignant prostate fibroblasts (NPFs) from 35 patients with primary prostate cancer. Morphologically, CAFs had more aligned stress fibres, and larger and more elongated nuclei, based on quantitative image analysis of confocal microscopy images. In addition, single-cell mechanical measurements using real-time deformability cytometry showed that CAFs are larger and stiffer than NPFs. These changes were consistent across patients and validated with atomic force microscopy. A combined morphomechanical score encompassing these features was significantly associated with patient outcome. In transcriptomic analyses, the score was correlated with microtubule dynamics and a myofibroblast phenotype. Importantly, we also demonstrated that morphomechanical features of prostate fibroblasts are modified by approved treatments for prostate cancer, such as docetaxel, and other small molecular inhibitors, such as axitinib. In summary, changes in cellular morphomechanical properties are a consistent feature of CAFs and associated with patient outcome. Moreover, cellular morphomechanical properties can be therapeutically targeted, potentially providing a new strategy for manipulating the TME to control cancer progression. ### Competing Interest Statement The authors have declared no competing interest.
Rxiv mechanobio

📰 "Reduced gap junction coupling amplifies the effects of cardiomyocyte variability and destabilizes the heartbeat"
biorxiv.org/content/10.1101/20 #Mechanical #Cell

bioRxiv · Reduced gap junction coupling amplifies the effects of cardiomyocyte variability and destabilizes the heartbeatCardiomyocytes exhibit significant cell-to-cell variability due to differences in protein expression and post-translational modifications in both the cell membrane and the intracellular machinery. Resulting variability in action potential propagation and configuration have been proposed to promote arrhythmia. However, such effects may be suppressed by tight electrical coupling of cells in the healthy heart, but not during pathological conditions where gap junction function is impaired. To investigate this question, we employed a cell-based mathematical model of cardiac electrophysiology, in which we systematically modified both the properties of individual cells within the array, and inter-cellular electrical connectivity (gap junctions). Despite the inclusion of marked variation in properties between cells, we observed electrical homogeneity across the array when cells were well coupled. In contrast, lower and/or more variable gap junction connectivity resulted in nonhomogeneous action potential configuration, and irregular timing of both the depolarizing and repolarizing electrical wavefronts. Pro-arrhythmic early after-depolarizations also occurred under these conditions, linked to reopening of L-type calcium channels. These effects were effectively dampened in highly coupled cells. Nevertheless, baseline differences in calcium homeostasis were not negated by gap junction coupling, indicating a limit to which electrical connections can homogenize mechanical function. There are also physical limits to electrical convergence, as we observed that action potential differences persisted at the edges and corners of the array where there are fewer electrical contacts with neighbouring cells. This finding may have implications for arrhythmic susceptibility in the border zone neighbouring an infarction. In summary, our findings underscore the critical role of intercellular coupling in maintaining cardiac stability and highlight the importance of studying cardiomyocytes within a syncytium rather than in isolation. ### Competing Interest Statement The authors have declared no competing interest.
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