Cells cultured in 3D fibrous biopolymer matrices exert traction forces on their environment that induce deformations and remodeling of the fiber network. By measuring these deformations, the traction forces can be reconstructed if the mechanical properties of the matrix and the force-free matrix configuration are known. These requirements limit the applicability of traction force reconstruction in practice. In this study, we test whether force-induced matrix remodeling can instead be used as a proxy for cellular traction forces. We measure the traction forces of hepatic stellate cells and different glioblastoma cell lines and quantify matrix remodeling by measuring the fiber orientation and fiber density around these cells. In agreement with simulated fiber networks, we demonstrate that changes in local fiber orientation and density are directly related to cell forces. By resolving Rho-kinase (ROCK) inhibitor-induced changes of traction forces, fiber alignment, and fiber density in hepatic stellate cells, we show that the method is suitable for drug screening assays. We conclude that differences in local fiber orientation and density, which are easily measurable, can be used as a qualitative proxy for changes in traction forces. The method is available as an open-source Python package with a graphical user interface.

在 3D 纤维生物聚合物基质中培养的细胞对其环境施加牵引力，从而引起纤维网络的变形和重塑。通过测量这些变形，如果基体的机械特性和无力基体配置已知，则可以重建牵引力。这些要求限制了牵引力重建在实践中的适用性。在这项研究中，我们测试了力诱导的矩阵重塑是否可以用作细胞牵引力的代表。我们测量肝星状细胞和不同胶质母细胞瘤细胞系的牵引力，并通过测量这些细胞周围的纤维方向和纤维密度来量化基质重塑。与模拟纤维网络一致，我们证明局部纤维方向和密度的变化与细胞力直接相关。通过解决 Rho 激酶 (ROCK) 抑制剂引起的肝星状细胞牵引力、纤维排列和纤维密度的变化，我们表明该方法适用于药物筛选测定。我们的结论是，易于测量的局部纤维取向和密度的差异可以用作牵引力变化的定性代理。该方法可作为带有图形用户界面的开源 Python 包提供。