In biological processes such as embryonic development, wound healing, and cancer invasion, cells move in cohesive groups. These groups are often led by a so-called leader cell, which is thought to pull and direct the followers. New work by Ricard Alert of the Max Planck Institute for the Physics of Complex Systems and his experimental collaborators in the group of Xavier Trepat at the Institute for Bioengineering of Catalonia (IBEC) now shows that the local action of a leader is not enough to guide the migration of cell groups. Instead, the researchers show that mechanical coordination across the entire cell group is needed for the group to move.
To test whether leader cells can pull others, the scientists used genetically-modified cells that turn into leaders when illuminated with blue light. In this way, the team could create leader cells on demand. The researchers then studied whether leader cells could act as the locomotive of small cell trains, up to four cells long. They found that a leader cell can robustly drag one follower but not longer cell trains. Leader cells therefore need the contribution of followers to guide the group. Ricard Alert then developed a physical model that shows how the motion of cell trains arises from asymmetries in cellular traction forces across the entire cell train, in agreement with the team’s experimental measurements. The new work therefore challenges the notion of autonomous leader cells, and it shows that cells need to coordinate their forces to move in groups.
More details can be found in the
press release (PDF).
Leone Rossetti, Steffen Grosser, Juan Francisco Abenza, Léo Valon, Pere Roca-Cusachs, Ricard Alert, and Xavier Trepat. Optogenetic generation of leader cells reveals a force–velocity relation for collective cell migration, Nat. Phys. (2024)