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细胞如何在细胞聚集的扩散中流动。

How cells flow in the spreading of cellular aggregates.

机构信息

University Pierre and Marie Curie, University of Paris, Institut Curie, 75248 Paris Cedex 05, France;Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Unité Mixte de Recherche 168, Institut Curie, 75248 Paris Cedex 05, France;

University Pierre and Marie Curie, University of Paris, Institut Curie, 75248 Paris Cedex 05, France;Centre National de la Recherche Scientifique, Unité Mixte de Recherche 144, Institut Curie, 75248 Paris Cedex 05, France;

出版信息

Proc Natl Acad Sci U S A. 2014 Jun 3;111(22):8055-60. doi: 10.1073/pnas.1323788111. Epub 2014 May 16.

Abstract

Like liquid droplets, cellular aggregates, also called "living droplets," spread onto adhesive surfaces. When deposited onto fibronectin-coated glass or polyacrylamide gels, they adhere and spread by protruding a cellular monolayer (precursor film) that expands around the droplet. The dynamics of spreading results from a balance between the pulling forces exerted by the highly motile cells at the periphery of the film, and friction forces associated with two types of cellular flows: (i) permeation, corresponding to the entry of the cells from the aggregates into the film; and (ii) slippage as the film expands. We characterize these flow fields within a spreading aggregate by using fluorescent tracking of individual cells and particle imaging velocimetry of cell populations. We find that permeation is limited to a narrow ring of width ξ (approximately a few cells) at the edge of the aggregate and regulates the dynamics of spreading. Furthermore, we find that the subsequent spreading of the monolayer depends heavily on the substrate rigidity. On rigid substrates, the migration of the cells in the monolayer is similar to the flow of a viscous liquid. By contrast, as the substrate gets softer, the film under tension becomes unstable with nucleation and growth of holes, flows are irregular, and cohesion decreases. Our results demonstrate that the mechanical properties of the environment influence the balance of forces that modulate collective cell migration, and therefore have important implications for the spreading behavior of tissues in both early development and cancer.

摘要

类似于液滴,细胞聚集体也被称为“活液滴”,会扩散到附着的表面上。当它们沉积在纤维连接蛋白涂层的玻璃或聚丙烯酰胺凝胶上时,它们会通过突出细胞单层(前导膜)来粘附和扩散,该单层会围绕液滴扩展。扩散的动力学源于膜外周高迁移性细胞施加的拉力与两种类型的细胞流相关的摩擦力之间的平衡:(i)渗透,对应于细胞从聚集体进入膜内;(ii)膜扩展时的滑移。我们通过对单个细胞进行荧光追踪和对细胞群体进行粒子成像测速法,来描绘聚集体内的这些流场。我们发现,渗透仅限于聚集体边缘宽度为 ξ(大约几个细胞)的狭窄环内,并调节扩散的动力学。此外,我们发现,随后的单层扩展严重依赖于基底的刚性。在刚性基底上,单层中的细胞迁移类似于粘性液体的流动。相比之下,随着基底变得更软,张力下的膜会变得不稳定,产生空洞的成核和生长,流动变得不规则,凝聚力降低。我们的结果表明,环境的力学性质会影响调节细胞集体迁移的力的平衡,因此对早期发育和癌症中组织的扩散行为具有重要意义。

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