Model depicting the mechanism by which tether formation reduces the force on adhesive bonds.
(A) A cell adherent within a flow field experiences a hydrodynamic shear force (Fs) that generates a torque (Ts) about the centroid of the cell. In order for the cell to remain stably adherent, the force of the adhesive bond (Fb) must oppose the shear force (Fs) in an equal and opposite manner. The ability of Fb to oppose Fs is in part dependent on the off rate of this adhesive interaction. Bonds that have an intrinsically rapid dissociation rate, such as the GP Ib/V/IX–VWF interaction, are unable to oppose FS, leading to cell translocation in the direction of flow. (B) Tether formation between the cell body and the adhesive surface gives mechanical advantage to the adhesive bond. The bond force Fb is composed of both horizontal and vertical components, dependent on the angle θ, to which it is applied at the adhesive surface. Tether formation increases the horizontal component of Fb (Fbcosθ) opposing Fs. In the case of a stationary cell within a flow field, the horizontal component of Fb must be equal and opposite to Fs. As the tether length increases, the proportion of Fb directly opposing Fs increases, thereby increasing the likelihood that the adhesive contact will remain stable. It should be noted that this model deals with the static situation in which no work is done. However, the dynamic process of tether formation, that is elongation of the plasma membrane, potentially involves considerable work, with the elastic energy stored in the tether also opposing the applied shear force.
