Computational modeling of three-dimensional ECM-rigidity sensing to guide directed cell migration
Computational modeling of three-dimensional ECM-rigidity sensing to guide directed cell migration
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DOI：
10.1073/pnas.1717230115
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发表时间：
2018-01-16
影响因子：
11.1
通讯作者：
Asada, H. Harry
中科院分区：
文献类型：
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作者：
Kim, Min-Cheol;Silberberg, Yaron R.;Asada, H. Harry
丝状伪足在感知周围细胞外基质 (ECM) 的化学和机械信号方面发挥着关键作用。然而，由于丝状伪足与周围 3D ECM 纤维之间的动态相互作用，局部 ECM 硬度的丝状伪足机械传感仍然缺乏定量理解。在这里，我们提出了一种基于弹性和离散 ECM 纤维理论来表征丝状伪足感知的 ECM 刚度的方法。我们已将此方法应用于丝状机械传感模型，用于预测定向细胞向更硬的 ECM 迁移。该模型为我们提供了当丝状足与周围的 ECM 纤维结合时力和位移的分布以及丝状足尖端附近的变化时间率。通过汇总 3D ECM 每个局部区域的这些效应，我们表达了细胞感知到的局部 ECM 刚度，并解释了细胞杜罗轴机制中的极性。
Filopodia have a key role in sensing both chemical and mechanical cues in surrounding extracellular matrix (ECM). However, quantitative understanding is still missing in the filopodial mechanosensing of local ECM stiffness, resulting from dynamic interactions between filopodia and the surrounding 3D ECM fibers. Here we present a method for characterizing the stiffness of ECM that is sensed by filopodia based on the theory of elasticity and discrete ECM fiber. We have applied this method to a filopodial mechanosensing model for predicting directed cell migration toward stiffer ECM. This model provides us with a distribution of force and displacement as well as their time rate of changes near the tip of a filopodium when it is bound to the surrounding ECM fibers. Aggregating these effects in each local region of 3D ECM, we express the local ECM stiffness sensed by the cell and explain polarity in the cellular durotaxis mechanism.