The unique nonlinear mechanics of the fibrous extracellular matrix (ECM) facilitates long-range cell-cell mechanical communications that would be impossible for linear elastic substrates. Past research has described the contribution of two separated effects on the range of force transmission, including ECM elastic nonlinearity and fiber alignment. However, the relation between these different effects is unclear, and how they combine to dictate force transmission range is still elusive. Here, we combine discrete fiber simulations with continuum modeling to study the decay of displacements induced by a contractile cell in fibrous networks. We demonstrate that fiber nonlinearity and fiber reorientation both contribute to the strain-induced elastic anisotropy of the cell's local environment. This elastic anisotropy is a "lumped" parameter that governs the slow decay of displacements, and it depends on the magnitude of applied strain, either an external tension or an internal contraction, as a model of the cell. Furthermore, we show that accounting for artificially prescribed elastic anisotropy dictates the decay of displacements induced by a contracting cell. Our findings unify previous single effects into a mechanical theory that explains force transmission in fibrous networks. This work may provide insights into biological processes that involve communication of distant cells mediated by the ECM, such as those occurring in morphogenesis, wound healing, angiogenesis, and cancer metastasis. It may also provide design parameters for biomaterials to control force transmission between cells as a way to guide morphogenesis in tissue engineering.

中文翻译：

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弹性各向异性控制细胞引起的位移范围

纤维细胞外基质 (ECM) 独特的非线性力学促进了长距离的细胞间机械通讯，而这对于线弹性基材来说是不可能的。过去的研究描述了两种独立效应对力传输范围的贡献，包括 ECM 弹性非线性和纤维对齐。然而，这些不同效应之间的关系尚不清楚，它们如何结合来决定力的传递范围仍然难以捉摸。在这里，我们将离散纤维模拟与连续模型相结合，以研究由纤维网络中的收缩细胞引起的位移衰减。我们证明了纤维非线性和纤维重新定向都有助于细胞局部环境的应变诱导的弹性各向异性。这种弹性各向异性是一个“集总” 控制位移缓慢衰减的参数，它取决于施加的应变的大小，外部张力或内部收缩，作为细胞模型。此外，我们表明，考虑人为规定的弹性各向异性决定了收缩细胞引起的位移衰减。我们的研究结果将以前的单一效应统一为一个机械理论，解释了纤维网络中的力传递。这项工作可能提供对涉及由 ECM 介导的远距离细胞通讯的生物学过程的见解，例如发生在形态发生、伤口愈合、血管生成和癌症转移中的那些。它还可以为生物材料提供设计参数，以控制细胞之间的力传递，作为指导组织工程形态发生的一种方式。