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coated cover slide, reported unbinding forces of 110-170 pN, bond lifetime
of 50 seconds and a Bell model barrier width of 2.5 Å.
91
Later work by Hanley
et al.
, using a more physiological ligand expressed on polymorphonuclear
leukocytes, revealed a similar barrier width but much shorter lifetime (5
seconds). 92 Work by Evans' (using micropipette) and Moy's groups reported
that selectin-ligand dissociation overcomes two activation barriers.
62,63
Compared with activated integrins, a majority of selectin-ligand bonds
have shorter lifetime, which perhaps correlate with the rolling behaviour
selectin mediates ( Fig. 11.7 ) . A series of studies by the group of Cheng Zhu
indicated small pulling force could prolong the lifetime of P-selectin-ligand
bonds, whereas force higher than 20 pN shortened the bond lifetime. Such a
catch-slip bond behaviour could account for the “shear threshold” effect in
selectin-mediated cell rolling. 23 To explain the catch bond phenomenon, the
same group later proposed a sliding rebinding model, where force triggers
two molecules sliding against each other, thereby increasing the afinity by
initiating more intermolecular interactions.
93
(a)
(b)
(c)
Figure 11.7. Adhesion strength of leukocyte adhesion complexes, L-selectin/sLeX
and high afinity integrin
A L B 2 /ICAM-1. (a) Dynamic force spectra of the interactions
(symbols, mean ± SEM) showing two loading rate regimes, a signature of two barriers.
Solid lines represent the best its of the Bell-Evans model [ Eq. (11.6) ] to each regime.
The itted parameters are shown in Table 11.1 * . (b) Force-dependent lifetimes
calculated from the itted parameters. (c) Energy landscape of the interactions.
The energy levels of the bound states were arbitrary chosen. The energy difference
between the inner (1) and outer (2) barriers was obtained from
$$ G 1,2 =
k B T ln(
T 02 /
T
01 ). Compared with the integrin interaction, the selectin well was wider, i.e. more
affected by force, and with shorter lifetime at zero force, being thus better adapted for
its rolling function. 5,62
* The itted intrinsic lifetimes of the inner barriers were 0.001 seconds for L-selectin/sLeX
and 0.025 seconds for α L β 2 /ICAM-1.
 
 
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