A research led by the Institute for Bioengineering of Catalonia (IBEC), based in the Barcelona Science Park,  has studied the migratory movement of groups of cells using light control. The results, published in Nature Physics, show that there is no leader cell that directs the collective movement, as previously thought, but that all cells participate in the process. These findings are relevant to the design of treatments to stop tumour invasion or accelerate wound healing, physiological processes closely linked to cell migration.

In processes such as embryonic development, wound healing or cancer invasion, cells are known to move in groups in a coordinated way. Leading these groups of cells are so-called leader cells, which are highly mobile and seem to direct the migration of the whole group, just as groups of animals often organise themselves according to the instructions of a leader.

A study led by IBEC has attempted to generate leader cells in the laboratory using optogenetic control, in order to test whether there really are cells that direct this collective movement and cells that follow them, and how information is transmitted from one to the other in order to move in a coordinated way.

The research team used genetically modified cells that were able to follow the movement of blue light. Where the cell is illuminated by the light beam, the protein Rac1 is activated, causing a protrusion known as a lamellipodium, which facilitates cell movement.

In the model developed by the research team, cells are placed on a substrate consisting of a gel with a stiffness similar to that of body tissue, containing a linear pattern, so that groups of different numbers of cells are formed in a row following the pattern.  These ‘trains’ of cells are then illuminated with the blue light beam to study their collective movement.

‘We have created a kind of train with different carriages, which are the cells. What we observed is that the illuminated cells are not able to pull a minimum number of followers, so they don’t lead the movement. So, we don’t have a train, but each carriage has its own engine and controls its speed and acceleration, each individual cell is an active player in the collective movement,’ says Leone Rossetti, a former IBEC researcher and first author of the paper.

These experiments show that there is no leader cell that directs the collective behaviour, but that cells that were thought to be followers also participate in the movement.

These results are relevant when designing treatments to stop tumour invasion or accelerate wound healing. We will have to act on the whole set of cells involved in the movement, and not just on the single cell that we thought was leading the movement of the rest,’ explains the leader of the study, Xavier Trepat, researcher at the Department of Biomedicine of the Faculty of Medicine and Health Sciences of the University of Barcelona and ICREA research professor at  IBEC.

» For further information: IBEC website [+]
» Reference article: Rossetti, L., Grosser, S., Abenza, J.F. et al. Optogenetic generation of leader cells reveals a force–velocity relation for collective cell migration. Nat. Phys. (2024). DOI: https://doi.org/10.1038/s41567-024-02600-2