Dr Anne Reversat

Leukocytes are immune cells that move throughout the whole organism for protection against pathogens. Although most cells require transmembrane adhesion receptors, especially those of the integrin family, to migrate on 2D, observations in 3D environments reveal that amoeboid cells such as leukocytes can migrate fast despite very low adhesive forces. Here, by combining CRISPR-Cas9 gene editing, microenvironment engineering and videomicroscopy, we discover that leukocytes are able to migrate in the complete absence of transmembrane force coupling in complex structures. We show that the actin cytoskeleton generate mechanical forces by creating a fast retrograde flow hindered by environmental topography, creating retrograde shear forces that are sufficient to drive the cell body forwards. Those observations explain for the first time how leukocyte fast motility is performed in vivo in complex 3D environments completely autonomously from the chemical composition of the environment.