改变细胞迁移的最佳刚度。
Shifting the optimal stiffness for cell migration.
机构信息
Department of Biomedical Engineering, University of Minnesota, 312 Church Street SE, Minneapolis, Minnesota 55455, USA.
Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
出版信息
Nat Commun. 2017 May 22;8:15313. doi: 10.1038/ncomms15313.
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.
细胞迁移是许多生物学过程（包括伤口愈合和癌症进展）的核心，对环境硬度敏感，许多细胞类型表现出迁移最大的最佳硬度。在这里，我们提出了一种细胞迁移模拟器，可以通过改变活跃的分子马达和离合器的数量来预测最佳硬度。通过比较两种细胞类型（具有不同数量活跃马达和离合器的胚胎鸡前脑神经元（ECFN；最佳硬度约为 1 kPa）和 U251 神经胶质瘤细胞）的细胞牵引力和 F-肌动蛋白逆行流动，实验验证了这一预测。此外，该模型预测并实验证实，U251 神经胶质瘤细胞迁移、形态和 F-肌动蛋白逆行流动速率的最佳硬度可以通过同时抑制肌球蛋白 II 马达和整合素介导的黏附来降低。
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