Fig. 5.
The mean lifetimes of PSGL-1–P-selectin, GP-1–P-selectin, and b-sLeX–P-selectin bonds plotted as continuous functions of force (A) and correlation of the two-pathway model to the mean lifetimes measured for neutrophil and PSGL-1 bead tethers to P-selectin in a flow chamber under different shear rates (data from ref. 8) (B). (A) Needed to match histograms under steady ramp and jump/ramp force histories (see legend of Fig. 2 for PSGL-1–P-selectin and legend of Fig. 4 for GP-1–P-selectin and b-sLeX–P-selectin), the mean rates of failure are continuous functions of applied force, the reciprocals being equivalent to the mean lifetimes expected at constant force. The red dashed line defines the lifetime if restricted to dissociation along the high-impedance pathway for PSGL-1–P-selectin. (B) Using the force scale fβ = 18 pN for rate exponentiation along pathway 2, the two-pathway model was fit to the data from ref. 8, assuming that the cell and bead attachments in the flow chamber experiments were held by an average of two bonds. The solid black curve shows the lifetime for one bond predicted by the two-pathway parameters: k1rup ≈ 7/sec, k2rup = (0.45/sec) exp(f/18 pN), and a crossover in force at ≈15–20 pN. The dashed black curve shows the lifetime 〈t〉 expected for two of these bonds that equally share the force f and fail randomly; i.e., 〈t〉= [krup(f) + 2 krup(f/2)]/[2 krup(f) krup(f/2)], where krup(f) defines the failure rate for one bond.