Biomechanical analysis of collective cell migration in vivo

细胞迁移对于伤口愈合和免疫应答至关重要，并且在癌细胞入侵时被激活。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，这种现象与癌细胞在转移过程中的运动相呼应。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，我们将利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侵袭。细胞迁移可以与人的行走进行比较：两者都需要感知指示运动方向的信号以及用于运动的基质的机械特性。在人行道上行走和在沙滩上行走是不一样的。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，因为它适用于体内研究，以及用于运动的底物的分子和机械操作。此外，神经波峰以细胞簇的形式迁移，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。我们将在体内测量神经嵴迁移所需的基质硬度，并测试这些机械性能对控制细胞迁移起始及其方向性的要求。此外，我们将分析细胞如何感知基板的机械特性。据我们所知，这将是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具有广泛的意义。

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.