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J. Cell Biol.,
Volume 144, Number 1, January 11, 1999 185-200
The Center for Blood Research and Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115
Wall shear stress in postcapillary venules
varies widely within and between tissues and in response to inflammation and exercise. However, the
speed at which leukocytes roll in vivo has been shown to be almost constant within a wide range of wall shear
stress, i.e., force on the cell. Similarly, rolling velocities
on purified selectins and their ligands in vitro tend to
plateau. This may be important to enable rolling leukocytes to be exposed uniformly to activating stimuli on
endothelium, independent of local hemodynamic conditions. Wall shear stress increases the rate of dissociation of individual selectin-ligand tether bonds exponentially (, ) thereby destabilizing rolling. We find
that this is compensated by a shear-dependent increase
in the number of bonds per rolling step. We also find an
increase in the number of microvillous tethers to the
substrate. This explains (a) the lack of firm adhesion through selectins at low shear stress or high ligand density, and (b) the stability of rolling on selectins to wide
variation in wall shear stress and ligand density, in contrast to rolling on antibodies (). Furthermore, our
data successfully predict the threshold wall shear stress
below which rolling does not occur. This is a special
case of the more general regulation by shear of the
number of bonds, in which the number of bonds falls
below one.
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