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细胞群在体内沿自生刚度梯度的集体趋硬性迁移
作者:小柯机器人 发布时间:2021/12/12 20:14:53

英国伦敦大学 Roberto Mayor 团队取得一项新突破。他们发现细胞群在体内沿自生刚度梯度的集体趋硬性迁移。相关论文于2021年12月8日在线发表在《自然》杂志上。

在这里,研究人员发现非洲爪蟾的神经嵴(一个胚胎细胞群),在邻近的基板组织中自我产生一个刚度梯度,并通过趋硬性遵循这个梯度迁移。梯度随着神经嵴移动,神经嵴不断追逐高刚度基板后退的区域。从机制上讲,神经嵴通过 N-钙粘蛋白(N – cadherin)与基板的相互作用来诱导硬度梯度产生,并通过细胞与基质粘附来感知梯度,从而产生极化的Rac活性和肌动球蛋白收缩性来共同协调趋硬性。趋硬性与趋化性协同作用,协同极化细胞群的肌动球蛋白机器,以促进体内高效的定向集体细胞迁移。

这些结果表明,在体内存在着趋硬性和动态刚度梯度,并且化学信号和机械信号的梯度协同作用实现了细胞高效定向迁移。

据悉,细胞集体迁移是形态发生、伤口愈合和癌症侵袭的基础。在体内大多数定向迁移被归因于趋化性,即细胞遵循化学梯度迁移。细胞在体外也可以遵循刚度梯度迁移,这一过程被称为趋硬性,但在体内缺乏趋硬性的证据。

附:英文原文

Title: Collective durotaxis along a self-generated stiffness gradient in vivo

Author: Shellard, Adam, Mayor, Roberto

Issue&Volume: 2021-12-08

Abstract: Collective cell migration underlies morphogenesis, wound healing and cancer invasion1,2. Most directed migration in vivo has been attributed to chemotaxis, whereby cells follow a chemical gradient3,4,5. Cells can also follow a stiffness gradient in vitro, a process called durotaxis3,4,6,7,8, but evidence for durotaxis in vivo is lacking6. Here we show that in Xenopus laevis the neural crest—an embryonic cell population—self-generates a stiffness gradient in the adjacent placodal tissue, and follows this gradient by durotaxis. The gradient moves with the neural crest, which is continually pursuing a retreating region of high substrate stiffness. Mechanistically, the neural crest induces the gradient due to N-cadherin interactions with the placodes and senses the gradient through cell–matrix adhesions, resulting in polarized Rac activity and actomyosin contractility, which coordinates durotaxis. Durotaxis synergizes with chemotaxis, cooperatively polarizing actomyosin machinery of the cell group to prompt efficient directional collective cell migration in vivo. These results show that durotaxis and dynamic stiffness gradients exist in vivo, and gradients of chemical and mechanical signals cooperate to achieve efficient directional cell migration.

DOI: 10.1038/s41586-021-04210-x

Source: https://www.nature.com/articles/s41586-021-04210-x

期刊信息

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html