Flexible cells (squares) are less likely to detach as shear stress increases.

Leukocytes use glycoprotein ligands to grab onto selectins on blood vessel walls and roll along with the blood flow. The longer the cell can roll without detaching, the greater its chances are of responding to chemoattractants telling it to traverse the endothelium at a site of inflammation. Now, on page 787, Yago et al. show that flexibility helps a cell avoid detachment when circulatory forces are high.

As shear force increases with higher blood pressure and smaller vessel size, leukocytes can maintain a stable rolling velocity, an ability known as an automatic braking system (ABS). Artificial microspheres containing certain ligands also roll on selectins, but lack an ABS—under high forces, their rolling velocity increases, and they are more apt to detach. Recent discussion in the field has centered on whether this difference reflects a problem with ligands or their carriers: either the microsphere ligands may not be optimal for binding under high forces, or the microspheres may lack some structural feature of cells.

Yago et al. address this issue by using the same ligands on both microspheres and a hematopoietic cell type that does not express selectin ligands. Their results show that ABS is a function of the ability of the cell to change its shape, a feature not found in rigid microspheres. Cells made more flexible by depolymerizing actin rolled even more efficiently. Making cells stiffer by fixation or addition of a cholesterol chelator made cells roll more like microspheres. ABS efficiency may be improved through the flattening of a cell, placing more of its ligands in contact with selectin on endothelial cells. Rolling leukocytes are also known to extend long thin tethers at their trailing edge; these structures may reduce the force exerted on the rest of the cell. ▪