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dependent dissociation lifetimes. The approach interprets each point in the
force curve as an individual force clamp experiment. Thus, determining the
total duration for each acting force allows us to calculate an almost continuous
force-dependent lifetime. 70 A more sophisticated approach is the application
of the Jarzynski equality to directly reconstruct the energy landscape of
the interaction from force curves. This procedure has been applied in
measurements of protein unfolding and receptor-ligand interactions. 71,72 The
application of such model-free methods allows us to directly determine the
effect of force on bond lifetimes and brings us the possibility of validating
energy landscape models.
(a)
(b)
(c)
Figure 11.6. Effect of force on the energy landscape (top) and dissociation kinetics
(bottom) of receptor-ligand interactions. (a) Single energy barrier at position ( γ )
and height (
$ G ) under no force (blue solid line) and under an applied constant force
(red solid line). The orange dotted line represents the force applied to the bond. The
force-dependent lifetime presents a single exponential decay [Bell model, Eq. (11.2)].
(b) Energy landscape with two energy barriers under no force (blue solid line) and
under applied force (red solid line). The dotted line represents the force applied to
the bond. The lifetime presents two exponential decays. The outer barrier governs
the dissociation kinetics at low forces ( F <
$$ G 1,2 / γ ), while the inner barrier governs
the dissociation at high forces. (c) One of the possible mechanisms for catch bond
behaviour. Two low energy states with two dissociation pathways (blue solid line).
The cartoon relects a hypothetical allosteric effect of force, which would change the
conformational state of the receptor favouring the active, slow state. Low force would
tilt the energy landscape (red solid line) increasing the population of the slower,
active state, resulting in longer lifetimes (catch regime in the lifetime plot). Above
a force threshold, the bond would behave as a slip bond, with force accelerating
dissociation.
 
 
 
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