Single-Molecule Rupture Dynamics on Multidimensional Landscapes
Dr. Yohichi Suzuki
Department of Physics and Center for Theoretical Biological Physics
UC San Diego
ABSTRACT
Single-molecule biophysical tools permit measurements of the mechanical
response of individual biomolecules to external load, revealing details
that are typically lost when studied by ensemble methods. Kramers theory
of diffusive barrier crossing in one dimension has been used to derive
analytical solutions for the observables in such experiments, in
particular, for the force dependent lifetimes. We propose a minimalist
model that captures the effects of multidimensionality of the free energy
landscape on the kinetics of a single-molecule system under constant
applied force. The model predicts a rich spectrum of scenarios for the
response of the system to the applied force. Among the scenarios is the
conventional decrease in the lifetime with the force, as well as a
remarkable rollover in the lifetime with a seemingly counterintuitive
increase of the lifetime at low force followed by a decrease in the
lifetime at higher forces. Realizations of each of the predicted scenario
are discussed in various biological contexts. Our model demonstrates that
the rollover in the lifetime does not necessarily imply a discrete switch
between two coexisting pathways on the free energy landscape, and that the
rollover can also be realized for a dynamics as simple as that on a single
pathway with a single bound state. Our model leads to an analytical
solution that reproduces the entire spectrum of scenarios, including the
rollover, in the force-dependent lifetime, in terms of the microscopic
parameters of the system.
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