Figure 1.

Mechanotransduction during the adhesion cascade. The proteins that mediate rolling and arrest of T cells on endothelial cells during the adhesion cascade are mechanosensors, which are sensitive to and relies on the force of the shear flow. (A) During the early steps of the adhesion cascade, selectins at the tip of microvilli of T cells interact with their ligands at the surface of endothelial cells to mediate tethering and rolling. Shear force impose a tension on this bond and thereby induces a conformational change in the selectin headpiece, which gives to the selectin-ligand bond a catch-bond characteristic. (B) Integrins mediate arrest after rolling and firm adhesion to the endothelium. Shear force also plays an essential role in this multistep process. Inside-out signaling from selectins of from chemokine receptors induces a first conformational change that increases the affinity of integrins for ICAMs and anchors them to the cytoskeleton through the recruitment of talin. Shear force pulls ligand-bond integrins into a high affinity, open conformation and increases the life-time of the bond through a catch-bond process.