发表机构
Tel Aviv University（特拉维夫大学）
机构由 AI 辅助整理，请以论文原文为准。AI 中文总结
本研究结合光镊实验与三维有限元模型，揭示拉伸纤维凝胶中局部刚度各向异性受纤维厚度和网络连通性调控，并指出局部微观力学响应异于整体硬化行为。
AI 中文摘要
结缔组织中的细胞存在于细胞外基质（ECM）内，该基质由纤维网状结构组成，其表现出非线性的应变硬化行为，这种行为由弯曲主导的变形向拉伸主导的变形转变所驱动。虽然体相流变学能够捕捉宏观力学性质，但细胞会主动感知并响应其环境中的局部微尺度异质性和刚度各向异性。因此，表征ECM微观力学对于理解细胞所经历的力学信号至关重要。本研究通过结合实验和数值方法，量化了拉伸纤维凝胶中的局部刚度各向异性。实验方面，我们利用光镊微流变学测量了经受单轴拉伸的纤维蛋白凝胶中的局部刚度。凝胶在拉伸轴和垂直轴方向均表现出逐渐的局部硬化，其中沿拉伸轴的增加更为显著，从而产生局部各向异性。为了探究驱动这一现象的物理参数，我们开发了一个离散随机纤维网络的三维有限元模型，成功复现了实验中的局部硬化和各向异性。数值分析进一步揭示，在亚等静压区域内，纤维厚度和网络连通性均强烈影响局部各向异性：细长纤维和更高的连通性可将各向异性放大至一个数量级。这有助于形成高度各向异性的局部环境，从而在引导力学驱动的生物过程（如细胞迁移和趋硬性）中发挥重要作用。我们的模拟还表明，局部微观力学响应可能不同于材料的整体硬化行为，这凸显了在微观尺度上进行表征的必要性。
英文摘要
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.
