Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14434-9. doi: 10.1073/pnas.1207968109. Epub 2012 Jul 11.
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.
突起的形成是细胞迁移的一个必要步骤。在三维环境中和体内迁移的细胞可以形成各种各样的突起类型，包括由肌动蛋白聚合驱动的片状伪足和由收缩性驱动的泡状伪足。人们提出，能够在不同的突起之间转换的能力有助于在复杂环境中运动，并促进癌症的扩散。然而，到目前为止，突起形成的可塑性主要是在变形虫和间质迁移模式之间的转换的背景下进行研究的，这涉及到整个细胞形态的实质性变化。因此，泡状伪足和片状伪足之间转换的最小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。使用可以诱导形成泡状伪足或片状伪足的细胞，我们系统地评估了突起类型之间转换的力学要求和动力学。我们证明，在迁移细胞中，肌动蛋白突起性和肌动球蛋白收缩性之间的平衡的改变会导致泡状伪足和片状伪足之间的即时转换。转换发生时，细胞的整体形状、极性或细胞黏附性没有变化。此外，在微图案化表面上迁移过程中基质黏附力的变化也可以触发泡状伪足和片状伪足之间的快速转换。总之，我们的数据表明，迁移细胞形成的突起类型可以独立于整体细胞形态进行动态控制，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。
