Biomechanical analysis of collective cell migration in vivo

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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.