Experimental validation of biasing of
ddFLN4 and FIVAR unfolding
forces by the VHH:mCherry complex and implementation of correction
algorithm. (a, b) AFM-SMFS measurements on FIVAR domain with (a) Sdrg:Fg
complex (unbiased system) and (b) VHH:mCherry complex (biased system).
Experimental AFM setup, representative force trace, and the aligned
contour length histogram are shown. The unfolding of FIVAR domain
with an ∼31 nm increment, followed by the two-step unfolding
of the ddFLN4 FP domain with ∼35 nm increments could be identified
from the contour length histogram. (c) Dynamic force spectrum of FIVAR
unfolding forces obtained from both (a) unbiased system using SdrG:Fg
complex (blue) and (b) biased system using VHH:mCherry complex (red).
(d) Dynamic force spectrum of ddFLN4 unfolding forces obtained from
both (a) unbiased system using SdrG:Fg complex (blue) and (b) biased
system using VHH:mCherry complex (red). The most probable rupture
force and loading rates were fit using the Bell–Evans model
(dashed lines). Using the fitting approach based on minimizing η
residuals, we obtained new energy landscape parameters corresponding
to the black dashed line. In the right-hand-side plots of (c) and
(d), the black solid line represents the distribution after algorithmic
correction.