Biomechanical analysis of collective cell migration in vivo

体内集体细胞迁移的生物力学分析

• 批准号: BB/R00627X/1
• 负责人: Roberto Mayor
• 金额: $ 61.5万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR00627X%2F1
• 关键词: Biomechanical; analysis; collective; cell; migration

Cell migration is essential for wound healing and immune response, and it is activated during invasion of cancer cells. All these migratory cells exhibit the same behaviours as embryonic cells. For example, during embryonic development cells move throughout the body, a phenomenon echoed in the movements of cancer cells during metastasis. This has led researchers to suppose that the molecular mechanisms driving these processes may be similar. Therefore, we will study cell migration by using the neural crest cells, an embryonic cell population whose migratory behaviour is similar to the invasion of cancer cells. Cell migration can be compared with a person walking: both need to sense the signs that indicate the direction of movement as well as the mechanical properties of the substrate used for locomotion. It is not the same to walk on the pavement than to walk on sand. While the role of molecular signals in cell migration is comparatively well understood, how tissue mechanics influences migration in vivo remains unknown. Neural crest is the ideal system to study cell migration as it is amenable for in vivo studies, as well as for molecular and mechanical manipulations of the substrate used for locomotion. In addition neural crests migrate as clusters of cells, an intensely studied but poorly understood process called collective cell migration. We will measure the hardness of the substrate that is required for neural crest migration in vivo, and test the requirement of these mechanical properties to control the initiation of cell migration as well as its directionality. In addition we will analyse how cells sense the mechanical properties of the substrate. As far as we know, this will constitute the first study investigating the role of mechanical cues on collective cell migration performed in vivo, and it will have wide implications in understanding cell migration in many physiological situations.

细胞迁移对于伤口愈合和免疫应答是必不可少的，并且在癌细胞入侵期间被激活。所有这些迁移细胞都表现出与胚胎细胞相同的行为。例如，在胚胎发育过程中，细胞在全身移动，这一现象与癌细胞在转移过程中的移动相呼应。这使得研究人员假设驱动这些过程的分子机制可能是相似的。因此，我们将通过使用神经嵴细胞来研究细胞迁移，神经嵴细胞是一种胚胎细胞群，其迁移行为类似于癌细胞的入侵。细胞迁移可以与人行走进行比较：两者都需要感知指示运动方向的迹象以及用于运动的基质的机械性能。走在人行道上和走在沙滩上是不一样的。虽然分子信号在细胞迁移中的作用已经比较清楚，但组织力学如何影响体内迁移仍然未知。神经嵴是研究细胞迁移的理想系统，因为它适合于体内研究，以及用于运动的基质的分子和机械操纵。此外，神经嵴作为细胞簇迁移，这是一个被深入研究但知之甚少的过程，称为集体细胞迁移。我们将测量体内神经嵴迁移所需的基底硬度，并测试这些机械性能的要求，以控制细胞迁移的开始及其方向性。此外，我们将分析细胞如何感知基质的机械特性。据我们所知，这将构成第一个研究机械线索在体内集体细胞迁移中的作用的研究，它将对理解许多生理情况下的细胞迁移产生广泛的影响。

项目成果

RanBP1 plays an essential role in directed migration of neural crest cells during development

RanBP1 在神经嵴细胞发育过程中的定向迁移中发挥重要作用

• DOI: 10.1101/2022.05.05.490747
• 发表时间: 2022
• 作者: Barriga E

Characterization of Pax3 and Sox10 transgenic Xenopus laevis embryos as tools to study neural crest development.

• DOI: 10.1016/j.ydbio.2018.02.020
• 发表时间: 2018-12-01
• 期刊: Developmental biology
• 影响因子: 2.7
• 作者: Alkobtawi M;Ray H;Barriga EH;Moreno M;Kerney R;Monsoro-Burq AH;Saint-Jeannet JP;Mayor R
• 通讯作者: Mayor R

Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo.

• DOI: 10.1038/nature25742
• 发表时间: 2018-02-22
• 期刊: Nature
• 影响因子: 64.8
• 作者: Barriga EH;Franze K;Charras G;Mayor R
• 通讯作者: Mayor R

Adjustable viscoelasticity allows for efficient collective cell migration.

• DOI: 10.1016/j.semcdb.2018.05.027
• 发表时间: 2019-09
• 期刊: Seminars in cell & developmental biology
• 影响因子: 7.3
• 作者: Barriga EH;Mayor R
• 通讯作者: Mayor R