  The quaternary structure of Filamin A (FLNa) 16-23 was recently shown to
exhibit multiple domain-domain interactions that lead to a propeller-like
construction. Here we present single molecule force spectroscopy experiments to
show a wide variety of mechanical responses of this molecule and compare it
with its linear counterpart FLNa 1-8. The compact structure of FLNa 16-23 leads
to a broad distribution of rupture forces and end-to-end lengths in the
force-extension mode and multiple unraveling timescales in the force-clamp
mode. Moreover, a subset of force-extension trajectories reveals a mechanical
hierarchy in which the rupture of domain-domain interactions at high forces
(200 pN) liberates the unfolding of individual domains at low forces (100 pN).
This mechanism may also explain the order of magnitude difference in the rates
of the biexponential fits to the distribution of unfolding dwell times under
force-clamp. Overall, FLNa 16-23 under a force of 100 pN is more compliant than
the linear FLNa 1-8. Since a physiological role of FLNa is to crosslink actin
filaments, this range of responses allows it to accommodate a broad spectrum of
forces exerted by the cell and its environment.
