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Mechanisms of 3D cell migration.
Nature Reviews Molecular Cell Biology ( IF 112.7 ) Pub Date : 2019-10-03 , DOI: 10.1038/s41580-019-0172-9
Kenneth M Yamada 1 , Michael Sixt 2
Affiliation  

Cell migration is essential for physiological processes as diverse as development, immune defence and wound healing. It is also a hallmark of cancer malignancy. Thousands of publications have elucidated detailed molecular and biophysical mechanisms of cultured cells migrating on flat, 2D substrates of glass and plastic. However, much less is known about how cells successfully navigate the complex 3D environments of living tissues. In these more complex, native environments, cells use multiple modes of migration, including mesenchymal, amoeboid, lobopodial and collective, and these are governed by the local extracellular microenvironment, specific modalities of Rho GTPase signalling and non-muscle myosin contractility. Migration through 3D environments is challenging because it requires the cell to squeeze through complex or dense extracellular structures. Doing so requires specific cellular adaptations to mechanical features of the extracellular matrix (ECM) or its remodelling. In addition, besides navigating through diverse ECM environments and overcoming extracellular barriers, cells often interact with neighbouring cells and tissues through physical and signalling interactions. Accordingly, cells need to call on an impressively wide diversity of mechanisms to meet these challenges. This Review examines how cells use both classical and novel mechanisms of locomotion as they traverse challenging 3D matrices and cellular environments. It focuses on principles rather than details of migratory mechanisms and draws comparisons between 1D, 2D and 3D migration.

中文翻译:

3D细胞迁移的机制。

细胞迁移对于生理过程至关重要,这些生理过程包括发育,免疫防御和伤口愈合。它也是癌症恶性肿瘤的标志。成千上万的出版物阐明了在平坦的玻璃和塑料二维平面上迁移的培养细胞的详细分子和生物物理机制。然而,关于细胞如何成功地在活体组织的复杂3D环境中导航的了解还很少。在这些更复杂的自然环境中,细胞使用多种迁移模式,包括间充质,变形虫,肺足和集体迁移,这些迁移受局部细胞外微环境,Rho GTPase信号传导的特定方式和非肌肉肌球蛋白收缩性的控制。通过3D环境进行迁移具有挑战性,因为它需要细胞挤压复杂或密集的细胞外结构。这样做需要针对细胞外基质(ECM)的机械特征或其重塑进行特定的细胞适应。此外,除了在各种ECM环境中导航并克服细胞外壁垒外,细胞还经常通过物理和信号相互作用与邻近的细胞和组织相互作用。因此,细胞需要呼吁广泛多样的机制来应对这些挑战。这篇评论探讨了细胞在穿越具有挑战性的3D矩阵和细胞环境时如何利用经典和新颖的运动机制。它侧重于原理而不是迁移机制的细节,并在1D,2D和3D迁移之间进行了比较。
更新日期:2019-10-03
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