Cell mechanics control rapid transitions between blebs and lamellipodia during migration
Cell mechanics control rapid transitions between blebs and lamellipodia during migration
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DOI：
10.1073/pnas.1207968109
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发表时间：
2012-09-04
影响因子：
11.1
通讯作者：
Paluch, Ewa
中科院分区：
文献类型：
--
作者：
Bergert, Martin;Chandradoss, Stanley D.;Paluch, Ewa
蛋白质的形成是细胞迁移过程中的重要步骤。细胞在三维环境和体内迁移可以形成各种各样的突起类型，包括肌动蛋白聚合驱动的板状伪足和收缩驱动的水泡。已经提出了在不同突起之间切换的能力，以促进复杂环境中的运动性并促进癌症传播。然而，到目前为止，突起形成的可塑性主要是在变形虫和间充质迁移模式之间的过渡的背景下研究的，这涉及到整体细胞形态的实质性变化。因此，水泡和板状伪足之间的过渡的最低要求，以及它们发生的时间尺度，仍然未知。为了解决这些问题，我们在单细胞水平上研究了细胞迁移过程中的突起转换。使用可以诱导形成水泡或板状伪足的细胞，我们系统地评估了突出类型之间切换的机械要求以及动力学。我们证明，肌动蛋白的伸缩性和肌动球蛋白的收缩性之间的平衡转移导致迁移细胞中的水泡和板状伪足之间的立即过渡。转换发生在没有改变全球细胞的形状，极性，或细胞粘附。此外，在微图案化表面上的迁移期间，也可以在基底粘附力变化时触发水泡和板状伪足之间的快速转变。总之，我们的数据显示，迁移细胞形成的突起类型可以独立于整体细胞形态动态控制，这表明突起形成是控制细胞迁移可塑性的调控网络中的一个自主模块。
Protrusion formation is an essential step during cell migration. Cells migrating in three-dimensional environments and in vivo can form a wide variety of protrusion types, including actin polymerization-driven lamellipodia, and contractility-driven blebs. The ability to switch between different protrusions has been proposed to facilitate motility in complex environments and to promote cancer dissemination. However, plasticity in protrusion formation has so far mostly been investigated in the context of transitions between amoeboid and mesenchymal migration modes, which involve substantial changes in overall cell morphology. As a result, the minimal requirements of transitions between blebs and lamellipodia, as well as the time scales on which they occur, remain unknown. To address these questions, we investigated protrusion switching during cell migration at the single cell level. Using cells that can be induced to form either blebs or lamellipodia, we systematically assessed the mechanical requirements, as well as the dynamics, of switching between protrusion types. We demonstrate that shifting the balance between actin protrusivity and actomyosin contractility leads to immediate transitions between blebs and lamellipodia in migrating cells. Switching occurred without changes in global cell shape, polarity, or cell adhesion. Furthermore, rapid transitions between blebs and lamellipodia could also be triggered upon changes in substrate adhesion during migration on micropatterned surfaces. Together, our data reveal that the type of protrusion formed by migrating cells can be dynamically controlled independently of overall cell morphology, suggesting that protrusion formation is an autonomous module in the regulatory network that controls the plasticity of cell migration.