Generating leader cells with light

In processes like embryonic development, wound healing, and cancer invasion, cells often migrate in groups, exhibiting remarkable coordination. Traditionally, it has been thought that “leader cells” guide this collective movement, much like a leader directs a group of animals.In our latest study, we set out to challenge this idea by using optogenetic tools to investigate the phenomenon of collective cell migration. We aimed to determine whether certain cells truly act as leaders while others follow and to uncover how information flows within the group to enable coordinated movement.To achieve this, we engineered cells that respond to blue light. When illuminated, these cells activate the Rac1 protein, causing them to form lamellipodia—protrusions that drive movement. We placed these cells on substrates designed to mimic the stiffness of human tissue, arranging them into linear “trains” to study their behavior under controlled conditions.Our experiments revealed surprising results: cells previously thought to be followers actively contribute to the group’s movement. This finding challenges the long-held view that leader cells alone direct collective migration. Instead, we discovered that the coordination arises from shared dynamics across all cells.One of the biggest challenges we faced was understanding the relationship between the forces cells generate and the speeds at which they move. Collaborating with Dr. Ricard Alert from the Max Planck Institute for the Physics of Complex Systems, we developed a mathematical model to bridge this gap. Our model describes how the spatial distribution of forces within a group translates into their collective migration speed.These findings may have important implications for designing therapies to stop tumor invasion or accelerate wound healing. Our work suggests that effective treatments must target the entire group of migrating cells, rather than focusing solely on presumed leader cells.