Fiber alignment in 3D collagen networks as a biophysical marker for cell contractility.
Fiber alignment in 3D collagen networks as a biophysical marker for cell contractility.
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3D 胶原蛋白网络中的纤维排列作为细胞收缩性的生物物理标记。
DOI：
10.1016/j.matbio.2023.11.004
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
R
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作者：
Böhringer,David;Bauer,Andreas;Moravec,Ivana;Bischof,Lars;Kah,Delf;Mark,Christoph;Grundy,ThomasJ;Görlach,Ekkehard;O'Neill,GeraldineM;Budday,Silvia;Strissel,PamelaL;Strick,Reiner;Malandrino,Andrea;Gerum,Richard;Mak,Michael;R
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，从而诱导纤维网络的变形和重塑。通过测量这些变形，牵引力可以重建，如果矩阵和力自由矩阵配置的机械性能是已知的。这些要求限制了牵引力重构在实际中的适用性。在这项研究中，我们测试力诱导的基质重塑是否可以代替细胞牵引力的代理。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，我们证明了局部纤维取向和密度的变化与细胞力直接相关。通过解决Rho-激酶（ROCK）激酶诱导的肝星状细胞中的牵引力，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试验。我们的结论是，在当地的纤维取向和密度，这是很容易测量的差异，可以作为一个定性的代理牵引力的变化。该方法可作为具有图形用户界面的开源Python包使用。
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.