Filamin A Is Essential for Active Cell Stiffening but not Passive Stiffening under External Force
Filamin A Is Essential for Active Cell Stiffening but not Passive Stiffening under External Force
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DOI：
10.1016/j.bpj.2009.02.035
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发表时间：
2009-05-20
影响因子：
3.4
通讯作者：
Weitz, D. A.
中科院分区：
文献类型：
--
作者：
Kasza, K. E.;Nakamura, F.;Weitz, D. A.
细胞的材料特性决定了机械力如何通过细胞传递并被细胞感知。某些类型的细胞在大的外力下被动地伸展，但它们也可以改变自己的刚度以响应局部的机械环境或生化线索。在这里，我们表明，肌动蛋白结合蛋白细丝蛋白A是必不可少的积极硬化的细胞涂在胶原蛋白涂层基板。这似乎是由于在缺乏细丝蛋白A的情况下，建立大的内部收缩应力的能力降低。为了证明这一点，我们比较了细丝蛋白A表达不同的两种人黑色素瘤细胞系的材料特性和收缩性。细丝蛋白A缺乏的M2细胞比细丝蛋白A充足的A7细胞更柔软，并且对基质施加小得多的收缩应力，即使M2细胞具有相似水平的磷酸化肌球蛋白11轻链并且仅稍微降低粘附强度。与A7细胞相反，M2细胞的硬度和收缩性对肌球蛋白抑制药物或基质的硬度不敏感。然而，令人惊讶的是，细丝蛋白A在大的外力下不需要被动硬化。
The material properties of a cell determine how mechanical forces are transmitted through and sensed by that cell. Some types of cells stiffen passively under large external forces, but they can also alter their own stiffness in response to the local mechanical environment or biochemical cues. Here we show that the actin-binding protein filamin A is essential for the active stiffening of cells plated on collagen-coated substrates. This appears to be due to a diminished capability to build up large internal contractile stresses in the absence of filamin A. To show this, we compare the material properties and contractility of two human melanoma cell lines that differ in filamin A expression. The filamin A-deficient M2 cells are softer than the filamin A-replete A7 cells, and exert much smaller contractile stresses on the substratum, even though the M2 cells have similar levels of phosphorylated myosin 11 light chain and only somewhat diminished adhesion strength. In contrast to A7 cells, the stiffness and contractility of M2 cells are insensitive to either myosin-inhibiting drugs or the stiffness of the substratum. Surprisingly, however, filamin A is not required for passive stiffening under large external forces.