Fluid Stresses on the Membrane of Migrating Leukocytes

We recently demonstrated that migrating human leukocytes respond to normal physiologic fluid stresses (∼1 dyn/cm 2 ) by active control of local cytoplasmic extensions (pseudopods). To better understand the governing mechanisms of this response, we determined the fluid stress distributions on individual migrating leukocytes whose shapes were reconstructed with serial confocal microscopy. The flow over adherent leukocytes was computed by solution of the Stokes equation for plasma motion over the cell membrane. The fluid stresses are highest at the top of the cell and lowest in the substrate contact region. Pseudopods experience enhanced shear stresses but at lower values than at the top. Interestingly, leukocytes retract pseudopods in all regions and not only at sites with maximum fluid stresses. Therefore we hypothesized that sub-micron membrane folds (microvilli) serve to locally enhance the fluid stress on the cell. Using a separate model, we found that tips of microvilli experience greatly increased levels of stresses while the troughs between microvilli are shielded from fluid shear. This evidence suggests that the highly irregular shape of active leukocytes leads to fluid stresses that may stimulate local mechanosensory responses at many sites on the plasma membrane, even if they are located close to the cell-substrate contact region.