0.1 kilopascal difference for mechanophenotyping: soft matrix precisely regulates cellular architecture for invasion.
0.1 kilopascal difference for mechanophenotyping: soft matrix precisely regulates cellular architecture for invasion.
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DOI：
10.4161/bioa.29175
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发表时间：
2014-01-01
期刊：
影响因子：
--
通讯作者：
Gu, Zhizhan
中科院分区：
文献类型：
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作者：
Gu, Zhizhan
目前的知识将3D基质中的间充质细胞侵袭理解为基于细胞-基质粘附的细胞迁移和基质重塑的组合过程。除了细胞因子和趋化因子刺激的细胞侵袭外，基底细胞侵袭本身是一个复杂的过程，可以通过基质配体类型、密度、几何形状和刚度等来调节。理解这样一个复杂的生物过程需要通过一次仅改变一个或两个元素来精细地解剖简化的模型研究。过去的细胞运动性研究集中在基质硬度上，揭示了更硬的基质促进2D X-Y轴横向细胞运动性。在这里，我们评论最近的两项研究报告，而不是僵硬的矩阵，软矩阵促进基质蛋白水解和形成的侵入体样突起（ILP）沿沿着三维Z轴。这些研究还表明，软基质精确地调节正常细胞中在0.1千帕的硬度范围内的ILP形成。相反，恶性细胞如癌细胞可以响应于更宽范围的基质硬度而形成ILP。此外，不同的癌细胞响应于其自身有利的基质硬度范围以自发形成ILP。因此，我们在此提出了利用基质刚度精确调节ILP形成的想法，作为癌症转移预测和病理诊断的机械表型分析工具。
Current knowledge understands the mesenchymal cell invasion in a 3D matrix as a combined process of cell-to-matrix adhesion based cell migration and matrix remodeling. Excluding cell invasion stimulated by cytokines and chemokines, the basal cell invasion itself is a complicated process that can be regulated by matrix ligand type, density, geometry, and stiffness, etc. Understanding such a complicated biological process requires delicate dissections into simplified model studies by altering only one or two elements at a time. Past cell motility studies focusing on matrix stiffness have revealed that a stiffer matrix promotes 2D X-Y axis lateral cell motility. Here, we comment on two recent studies that report, instead of stiffer matrix, a softer matrix promotes matrix proteolysis and the formation of invadosome-like protrusions (ILPs) along the 3D Z axis. These studies also reveal that soft matrix precisely regulates such ILPs formation in the stiffness scale range of 0.1 kilopascal in normal cells. In contrast, malignant cells such as cancer cells can form ILPs in response to a much wider range of matrix stiffness. Further, different cancer cells respond to their own favorable range of matrix stiffness to spontaneously form ILPs. Thus, we hereby propose the idea of utilizing the matrix stiffness to precisely regulate ILP formation as a mechanophenotyping tool for cancer metastasis prediction and pathological diagnosis.