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  1. In tissue formation and repair, the epithelium undergoes complex patterns of motion driven by the active forces produced by each cell. Although the principles governing how the forces evolve in time are not yet clear, it is often assumed that the contractile stresses within the cell layer align with the axis defined by the body of each cell. Here, we simultaneously measured the orientations of the cell shape and the cell-generated contractile stresses, observing correlated, dynamic domains in which the stresses were systematically misaligned with the cell body. We developed a continuum model that decouples the orientations of contractile stress and cell body. The model recovered the spatial and temporal dynamics of the regions of misalignment in the experiments. These findings reveal that the cell controls its contractile forces independently from its shape, suggesting that the physical rules relating cell forces and cell shape are more flexible than previously thought. 
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    Free, publicly-accessible full text available December 1, 2025
  2. Free, publicly-accessible full text available March 1, 2025
  3. Slowing peritoneal spread in high-grade serous ovarian cancer (HGSOC) would improve patient prognosis and quality of life. HGSOC spreads when single cells and spheroids detach, float through the peritoneal fluid and take over new sites, with spheroids thought to be more aggressive than single cells. Using our in vitro model of spheroid collective detachment, we determine that increased substrate stiffness led to the detachment of more spheroids. We identified a mechanism where Piezo1 activity increased MMP-1/MMP-10, decreased collagen I and fibronectin, and increased spheroid detachment. Piezo1 expression was confirmed in omental masses from patients with stage III/IV HGSOC. Using OV90 and CRISPR-modifiedPIEZO1−/−OV90 in a mouse xenograft model, we determined that while both genotypes efficiently took over the omentum, loss of Piezo1 significantly decreased ascitic volume, tumor spheroids in the ascites, and the number of macroscopic tumors in the mesentery. These results support that slowing collective detachment may benefit patients and identify Piezo1 as a potential therapeutic target.

     
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    Free, publicly-accessible full text available April 26, 2025
  4. Dynamics of the cell shape and cell active stress in a monolayer. 
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  5. Abstract Soft bioinspired fiber networks offer great potential in biomedical engineering and material design due to their adjustable mechanical behaviors. However, existing strategies to integrate modeling and manufacturing of bioinspired networks do not consider the intrinsic microstructural disorder of biopolymer networks, which limits the ability to tune their mechanical properties. To fill in this gap, we developed a method to generate computer models of aperiodic fiber networks mimicking type I collagen ready to be submitted for additive manufacturing. The models of fiber networks were created in a scripting language wherein key geometric features like connectivity, fiber length, and fiber cross section could be easily tuned to achieve desired mechanical behavior, namely, pretension-induced shear stiffening. The stiffening was first predicted using finite element software, and then a representative network was fabricated using a commercial 3D printer based on digital light processing technology using a soft resin. The stiffening response of the fabricated network was verified experimentally on a novel test device capable of testing the shear stiffness of the specimen under varying levels of uniaxial pretension. The resulting data demonstrated clear pretension-induced stiffening in shear in the fabricated network, with uniaxial pretension of 40% resulting in a factor of 2.65 increase in the small strain shear stiffness. The strategy described in this article addresses current challenges in modeling bioinspired fiber networks and can be readily integrated with advances in fabrication technology to fabricate materials truly replicating the mechanical response of biopolymer networks. 
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  6. Abstract Fiber networks are the primary structural components of many biological structures, including the cell cytoskeleton and the extracellular matrix. These materials exhibit global nonlinearities, such as stiffening in extension and shear, during which the fibers bend and align with the direction of applied loading. Precise details of deformations at the scale of the fibers during strain stiffening are still lacking, however, as prior work has studied fiber alignment primarily from a qualitative perspective, which leaves incomplete the understanding of how the local microstructural evolution leads to the global mechanical behavior. To fill this gap, we studied how axial forces are transmitted inside the fiber network along paths called force chains, which continuously evolve during the course of deformation. We performed numerical simulations on two-dimensional networks of random fibers under uniaxial extension and shear, modeling the fibers using beam elements in finite element software. To quantify the force chains, we identified all chains of connected fibers for which the axial force was larger than a preset threshold and computed the total length of all such chains. To study the evolution of force chains during loading, we computed the derivative of the total length of all force chains with respect to the applied engineering strain. Results showed that the highest rate of evolution of force chains coincided with the global critical strain for strain stiffening of the fiber network. Therefore, force chains are an important factor connecting understanding of the local kinematics and force transmission to the macroscale stiffness of the fiber network. 
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  7. null (Ed.)
    We investigated an in vitro model for mesothelial clearance, wherein ovarian cancer cells invade into a layer of mesothelial cells, resulting in mesothelial retraction combined with cancer cell disaggregation and spreading. Prior to the addition of tumor cells, the mesothelial cells had an elongated morphology, causing them to align with their neighbors into well-ordered domains. Flaws in this alignment, which occur at topological defects, have been associated with altered cell density, motion, and forces. Here we identified topological defects in the mesothelial layer, and showed how they affected local cell density by producing a net flow of cells inward or outward, depending on defect type. At locations of net inward flow, mesothelial clearance was impeded. Hence, the collective behavior of the mesothelial cells, as governed by the topological defects, affected tumor cell clearance and spreading. Importantly, our findings were consistent across multiple ovarian cancer cell types, suggesting a new physical mechanism that could impact ovarian cancer metastasis. 
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