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PreprintarXiv licencearXiv

Local Strain-Dependent Anisotropy in Fibrous Networks

Abstract

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.

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BibTeX
@misc{koren2026local,
  title = {{Local Strain-Dependent Anisotropy in Fibrous Networks}},
  author = {Yoni Koren and Shahar Goren and Oren Tchaicheeyan and Ayelet Lesman},
  howpublished = {arXiv},
  year = {2026},
  month = sep,
  doi = {10.48550/arxiv.2609.13472},
  eprint = {2609.13472},
  archivePrefix = {arXiv},
  url = {https://arxiv.org/abs/2609.13472},
}
RIS
TY  - UNPB
TI  - Local Strain-Dependent Anisotropy in Fibrous Networks
AU  - Yoni Koren
AU  - Shahar Goren
AU  - Oren Tchaicheeyan
AU  - Ayelet Lesman
PY  - 2026
DA  - 2026/09/11
PB  - arXiv
DO  - 10.48550/arxiv.2609.13472
UR  - https://arxiv.org/abs/2609.13472
AB  - 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.
ER  -