Cells, like humans, vote and make decisions as a group, seeking information in order to make faster and better collective decisions to coordinate the development of new blood vessels. Researchers liken it to someone entering a dark, unfamiliar room and pointing their hands at the wall for a light switch. In the case of cells, long “fingers” are created and thus feel the environment. This allows them to quickly select the cell that detects the largest signal to become the leader μη sharp cell} that pushes the new blood vessel forward.

Molecule A binds to receptor B and causes motion C, a collective decision with the steps next to each other. At the beginning of this process, some endothelial cells along the outer existing blood vessel, turn into sharp cells with long finger-like protrusions on their surface, called filopodia, and are the first to move away from the existing vessel to form its head, new, sprouted vessel.

Many aspects of the synchronization and interactions of cells involved in this process, including how endothelial cells decide which of them should become alveoli, are not yet understood. Using computer simulations and studies of zebrafish embryos, the researchers found that filopodia begins to form on the cell surface before it binds to become a tip cell. The filopodia then spreads to the surrounding tissue and detects signals that can either cause the cell to become an acrostomy or inhibit it. This process of moving and detecting philopods is an active perceptual feedback loop. To stop the cells from becoming top cells, the neighbors send signals so that only one cell specializes.

If peak cell selection goes wrong or slows down, this can lead to abnormal vascular networks, restricting blood flow, which can contribute to diseases such as cancer, retinopathy and hereditary haemorrhagic telangiectasia. Greater understanding of how to accelerate or change the branching rate could therefore lead to new therapies that can regulate blood vessel density. This could also help create artificial organs or tissues as they also need dense networks of blood vessels.

This project gave a new perspective to the process of selecting cells with filopodia, but also opened the door to new research directions for understanding cell behavior.

SOURCE: King’s College London {Biological Sciences 08/02/2021}