The interplay of cell-cell and cell-substrate adhesion in collective cell migration.

Collective cell migration often involves notable cell-cell and cell-substrate adhesions and highly coordinated motion of touching cells. We focus on the interplay between cell-substrate adhesion and cell-cell adhesion. We show that the loss of cell-surface contact does not significantly alter the dynamic pattern of protrusions and retractions of fast migrating amoeboid cells (Dictyostelium discoideum), but significantly changes their ability to adhere to other cells. Analysis of the dynamics of cell shapes reveals that cells that are adherent to a surface may coordinate their motion with neighbouring cells through protrusion waves that travel across cell-cell contacts. However, while shape waves exist if cells are detached from surfaces, they do not couple cell to cell. In addition, our investigation of actin polymerization indicates that loss of cell-surface adhesion changes actin polymerization at cell-cell contacts. To further investigate cell-cell/cell-substrate interactions, we used optical micromanipulation to form cell-substrate contact at controlled locations. We find that both cell-shape dynamics and cytoskeletal activity respond rapidly to the formation of cell-substrate contact.