Cell Collectives –Who's in charge?

A better understanding of mechanical interactions between leaders and followers in migrating groups of cells.

28. August 2018

Wound healing, organogenesis and cancer development are only some of the processes in which cell collectives have to be on the move, e.g. to close an open wound on a finger. In these processes, leader cells guide the migrating group of cells behind them. Why and how do some cells become leaders while others remain followers? Scientists in the department of Cellular Biophysics led by Joachim Spatz at the Max Planck Institute for Medical Research in Heidelberg now report on new insights into collective cell migration and what determines leader cells.

Studying epithelial wound margins, they have found that leader cells emerge in three phases. During phase 0, followers start to pull on their future leaders. This induces their polarization and protrusion formation. In phase 1 the leader starts to pull on its followers. Affected cells are now prohibited from becoming leaders themselves, and the leader establishes its territory. The size of this territory is determined by the force the leader can exert on the migrating group. As the number of cells increases with margin movement in phase 2, some cells are left outside of the territory of the existing leaders. As a consequence, new leaders are formed in those areas.

This work shows that non-interfacial mechano-biological processes play a major role in the determination of leader cells and in the interplay between leaders and followers. Insights into the behavior of cells during wound healing, cancer development or metastatic invasion are crucial for understanding these processes; this might allow them to be manipulated, thus contributing to the development of therapies for various diseases or forms of injury.