A traction force threshold signifies metastatic phenotypic change in multicellular epithelia.
A traction force threshold signifies metastatic phenotypic change in multicellular epithelia.
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DOI：
10.1039/c9sm00733d
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发表时间：
2019-09
期刊：
影响因子：
3.4
通讯作者：
Yao Zhang;Xuechen Shi;Tiankai Zhao;Changjin Huang;Qiong Wei;Xin Tang;Lorraine C. Santy;M. Taher A. Saif;Sulin Zhang
中科院分区：
文献类型：
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作者：
Yao Zhang;Xuechen Shi;Tiankai Zhao;Changjin Huang;Qiong Wei;Xin Tang;Lorraine C. Santy;M. Taher A. Saif;Sulin Zhang
癌症转移被认为是一个遗传程序化的过程，通常由生化信号标记。在这里，使用细胞力学的细胞外基质控制，我们建立了细胞力阈值也可以标记HCT-8细胞集落的体外转移表型变化和恶性转化。我们观察到，对于延长的培养时间，HCT-8细胞集落分散成单个恶性细胞，并且转移样分散取决于细胞接种凝胶硬度和集落大小。细胞力显微镜显示凝胶硬度和集落大小也是调节细胞力的两个关键参数，表明细胞力与转移表型变化之间的相关性。使用我们最近开发的生物物理模型，我们构建了一个细胞外牵引相图的刚度大小的空间，充满了实验数据的殖民地的行为。从相图中，我们确定了一个相边界作为牵引力阈值，高于该阈值发生转移性表型转变，低于该阈值细胞集落保持凝聚力。我们的研究结果表明，牵引阈值可以被视为一个有效的机械标记的转移样分散和恶性转化的开始。
Cancer metastasis has been believed as a genetically programmed process that is commonly marked by biochemical signals. Here using extracellular matrix control of cellular mechanics, we establish that cellular force threshold can also mark in vitro metastatic phenotypic change and malignant transformation in HCT-8 cell colonies. We observe that for prolonged culture time the HCT-8 cell colonies disperse into individual malignant cells, and the metastatic-like dispersion depends on both cell-seeding gel stiffness and colony size. Cellular force microscopies show that gel stiffness and colony size are also two key parameters that modulate cellular forces, suggesting the correlations between the cellular forces and the metastatic phenotypic change. Using our recently developed biophysical model, we construct an extracellular traction phase diagram in the stiffness-size space, filled with experimental data on the colony behavior. From the phase diagram we identify a phase boundary as a traction force threshold above which the metastatic phenotypic transition occurs and below which the cell colonies remain cohesive. Our finding suggests that the traction threshold can be regarded as an effective mechano-marker for the onset of the metastatic-like dispersion and malignant transformation.