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Oren Tchaicheeyan

Publications and source records attributed to Oren Tchaicheeyan.

3 recordsLinked to original sources

Mechanical Clustering of Cells via the ExtraCellular Matrix

Tissues are composites of living cells and extracellular matrix (ECM), that jointly determine their unique mechanical behavior. Here, we experimentally demonstrate that contractile cells remodel the ECM by generating long-range bands of aligned and densified fibers that mechanically couple cells into multicellular clusters. Using a finite-element model, we quantify the collective mechanical interactions mediated by these ECM bands for various volume fractions of cells. The model incorporates contractile particles that mimic cell-active forces within a nonlinear biological gel, inducing stiffening internally rather than through external loading. We find that even a small volume fraction of contractile particles (approximately 10%), much below what is expected for percolation of sphere contacts, leads to internal stiffening, mediated by the high-concentrated stress bands between cells and is strongly dependent on the nonlinear mechanical response of the ECM. Percolation analysis of the band network reveals sharp transitions at a critical particle volume fraction, that aligns with the onset of internal stiffening. These results demonstrate that long-range interaction between contractile cells through the deformation of the medium has the potential to globally shape the structure and mechanics of the bulk gel, leading to a functional structure with modified properties. These modified macroscopic changes can define organizing principles in tissue patterning and morphogenesis.

cond-mat.soft↗

Local Strain-Dependent Anisotropy in Fibrous Networks

Cells in connective tissues reside within the extracellular matrix (ECM), which consists of a fibrous mesh that exhibits non-linear strain-stiffening behavior, driven by a transition from bending-to-stretching-dominated deformation. While bulk rheology captures macroscopic mechanical properties, cells actively sense and respond to local microscale heterogeneities and stiffness anisotropy in their environment. Characterizing ECM micromechanics is therefore essential for understanding the mechanical cues experienced by cells. This study quantifies local stiffness anisotropy in stretched fibrous gels by combining experimental and numerical approaches. Experimentally, we utilized optical tweezers microrheology to measure local stiffness in fibrin gels subjected to uniaxial stretch. The gels demonstrated gradual local stiffening along both the tensile and perpendicular axes, with a more profound increase along the tensile axis, resulting in local anisotropy. To investigate the physical parameters driving this phenomenon, we developed a 3D finite element model of a discrete random fiber network, successfully replicating the experimental local stiffening and anisotropy. Numerical analysis further revealed that within the sub-isostatic region, both fiber thickness and network connectivity strongly influence local anisotropy: slender fibers and higher connectivity amplify the anisotropy by up to an order of magnitude. This contributes to the formation of a highly anisotropic local environment, thereby playing a significant role in directing mechanically driven biological processes, such as cell migration and durotaxis. Our simulations also indicate that local micromechanical responses may differ from the material's global stiffening behaviors, highlighting the need for characterization at the microscopic scale.

cond-mat.soft↗

Nonlinear elasticity of the extracellular matrix fibers facilitates efficient inter-cellular mechanical communication

Biological cells embedded in fibrous matrices have been observed to form inter-cellular bands of dense and aligned fibers, through which they mechanically interact over long distances. Such matrix-mediated cellular interactions have been shown to regulate a variety of biological processes. The current study was aimed at exploring the effects of elastic nonlinearity of the fibers contained in the extracellular matrix (ECM) on the transmission of mechanical loads between contracting cells. Based on our biological experiments, we developed a finite-element model of two contracting cells embedded within a fibrous network. The individual fibers were modeled as showing either linear elasticity, compression-microbuckling, tension-stiffening or both of the latter. Compression-buckling resulted in smaller loads occurring in the ECM, but these were more directed toward the neighboring cell. The latter decreased with increasing cell-to-cell distance; when cells were >15 cell-diameters apart, no such inter-cellular interaction was observed. Tension-stiffening further contributed to directing the loads toward the neighboring cell, though to a smaller extent. The contraction of two neighboring cells resulted in mutual attraction forces, which were considerably increased by tension-stiffening, and decayed with increasing cell-to-cell distances. Nonlinear elasticity contributed also to the onset of force polarity on the cell boundary. The density and alignment of the fibers within the inter-cellular band were considerably greater when fibers buckled under compression, with tension-stiffening further contributing to this structural remodeling. Our model demonstrates the contribution of nonlinear elasticity of biological gels to directionality and efficiency of mechanical-signal transfer between distant cells.

physics.bio-ph↗