Shifting the optimal stiffness for cell migration.
Shifting the optimal stiffness for cell migration.
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DOI：
10.1038/ncomms15313
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发表时间：
2017-05-22
影响因子：
16.6
通讯作者：
Odde DJ
中科院分区：
文献类型：
--
作者：
Bangasser BL;Shamsan GA;Chan CE;Opoku KN;Tüzel E;Schlichtmann BW;Kasim JA;Fuller BJ;McCullough BR;Rosenfeld SS;Odde DJ
细胞迁移是包括伤口愈合和癌症进展在内的许多生物学过程的核心，它对环境僵硬很敏感，许多类型的细胞表现出最优的僵硬，此时迁移是最大的。在这里，我们提出了一个细胞迁移模拟器，它预测了一个最优的硬度，可以通过改变活跃的分子马达和离合器的数量来改变。通过比较具有不同活跃马达和离合器数量的两种细胞类型的细胞牵引和F-肌动蛋白逆行流动，这一预测得到了实验验证：胚胎鸡前脑神经元(ECFN；最佳∼1 kpa)和U251胶质瘤细胞(最佳∼100 kpa)。此外，该模型预测并实验证实，通过同时抑制肌球蛋白II马达和整合素介导的粘连，U251胶质瘤细胞迁移、形态和F-肌动蛋白逆行流速的最佳刚性可以转移到较低的刚性。细胞迁移对环境刚性很敏感，但细胞如何感知最佳刚性尚不清楚。在这里，作者建立了一个模型，该模型预测通过改变活跃的分子马达和离合器的数量可以改变最优值，并在两种细胞类型中验证了他们的模型。
Cell migration, which is central to many biological processes including wound healing and cancer progression, is sensitive to environmental stiffness, and many cell types exhibit a stiffness optimum, at which migration is maximal. Here we present a cell migration simulator that predicts a stiffness optimum that can be shifted by altering the number of active molecular motors and clutches. This prediction is verified experimentally by comparing cell traction and F-actin retrograde flow for two cell types with differing amounts of active motors and clutches: embryonic chick forebrain neurons (ECFNs; optimum ∼1 kPa) and U251 glioma cells (optimum ∼100 kPa). In addition, the model predicts, and experiments confirm, that the stiffness optimum of U251 glioma cell migration, morphology and F-actin retrograde flow rate can be shifted to lower stiffness by simultaneous drug inhibition of myosin II motors and integrin-mediated adhesions. Cell migration is sensitive to environmental stiffness, but how cells sense optimal stiffness is not known. Here the authors develop a model that predicts that the optimum can be shifted by altering the number of active molecular motors and clutches, and verify their model in two cell types.