Laboratory-Generated Leader Cells Reveal New Insights Into Cell Migration

A study published in the journal Nature Physics has succeeded in generating leader cells in the laboratory using optogenetic control, which combines genetic modification with light. The aim is to test whether there are cells that direct this collective movement and others that follow them, as well as to discover how information is transmitted from one to the other to move in coordination.

The study is led by Xavier Trepat, a researcher at the Department of Biomedicine of the Faculty of Medicine and Health Sciences of the University of Barcelona and ICREA research professor at the Institute for Bioengineering of Catalonia (IBEC), based at the Barcelona Science Park (PCB).

The team used genetically modified cells capable of following the movement of blue light. Where the cell is illuminated by the beam of light, the RAC1 gene is activated, causing a protrusion known as a lamellipodium, which facilitates cell movement.

In the model the team has designed, cells are placed on a substrate consisting of a gel with a stiffness equivalent to that of body tissues, containing a linear pattern, so that groups of different numbers of cells follow the pattern in a row. These “trains” of cells are then illuminated with the blue light beam to study their collective movement.

“We generate a kind of train made up of different carriages, which are the cells. What we observed is that the enlightened cells cannot pull a minimum number of followers, so they don’t lead the movement. Therefore, we don't have a train, but each carriage has its 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 indicate that there is no leader cell guiding the collective movement, but that cells that were thought to be followers also participate in the movement. “These results are very relevant for designing treatments to stop tumour invasion or accelerate wound healing. We now know that we will have to act in a way that affects the whole set of cells that take part in the movement, and not just the individual cell that we thought was leading the movement of the rest”, explains Xavier Trepat, leader of the study.

Reference: Rossetti L, Grosser S, Abenza JF, et al. Optogenetic generation of leader cells reveals a force–velocity relation for collective cell migration. Nat Phys. 2024. doi: 10.1038/s41567-024-02600-2

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