Traction force microscopy of migrating normal and H-ras transformed 3T3 fibroblasts

Traction force microscopy of migrating normal and H-ras transformed 3T3 fibroblasts
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DOI:
10.1016/s0006-3495(01)76145-0
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发表时间:
2001-04-01
影响因子:
3.4
通讯作者:
Dembo, M
Dembo, M
中科院分区:
生物学3区
文献类型:
--
作者:
Munevar, S;Wang, YL;Dembo, M

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细胞和基质之间的机械相互作用涉及从迁移到信号转导的重要细胞功能,一种新发展的技术,牵引力显微镜,使得可以可视化成纤维细胞施加的机械力的动态特性,包括大小,方向和剪切。在本研究中,这种分析适用于迁移正常和转化的3 T3细胞。对于正常细胞,板状伪足提供几乎所有向前运动的力。一个高剪切区将片状伪足与细胞体分开,表明它们是机械上不同的实体。前缘牵引力的时间和分布与当地的扩张活动没有明显的关系。然而,牵引力模式的变化往往先于移徙方向的变化。这些观察结果表明,细胞迁移的正面牵引机制,其中在前缘的动态牵引力主动向前拉细胞体。对于H-ras转化的细胞,口袋里的弱,短暂的牵引分散在小伪足,似乎对彼此的行为。剪切模式表明多个无序的机械结构域。弱的、协调不良的牵引力,加上弱的细胞-基质粘附,可能是H-ras转化细胞异常运动行为的原因。
Mechanical interactions between cell and substrate are involved in vital cellular functions from migration to signal transduction, A newly developed technique, traction force microscopy, makes it possible to visualize the dynamic characteristics of mechanical forces exerted by fibroblasts, including the magnitude, direction, and shear. In the present study such analysis is applied to migrating normal and transformed 3T3 cells. For normal cells, the lamellipodium provides almost all the forces for forward locomotion. A zone of high shear separates the lamellipodium from the cell body, suggesting that they are mechanically distinct entities. Timing and distribution of tractions at the leading edge bear no apparent relationship to local protrusive activities. However, changes in the pattern of traction forces often precede changes in the direction of migration. These observations suggest a frontal towing mechanism for cell migration, where dynamic traction forces at the leading edge actively pull the cell body forward. For H-ras transformed cells, pockets of weak, transient traction scatter among small pseudopods and appear to act against one another. The shear pattern suggests multiple disorganized mechanical domains, The weak, poorly coordinated traction forces, coupled with weak cell-substrate adhesions, are likely responsible for the abnormal motile behavior of H-ras transformed cells.