Theoretical studies of the kinetics of mechanical unfolding of cross-linked polymer chains and their implications for single-molecule pulling experiments

Abstract

We have used kinetic Monte Carlo simulations to study the kinetics of unfolding of cross-linked polymer chains under mechanical loading. As the ends of a chain are pulled apart, the force transmitted by each crosslink increases until it ruptures. The stochastic crosslink rupture process is assumed to be governed by first order kinetics with a rate that depends exponentially on the transmitted force. We have performed random searches to identify optimal crosslink configurations whose unfolding requires a large applied force (measure of strength) and/or large dissipated energy (measure of toughness). We found that such optimal chains always involve cross-links arranged to form parallel strands. T he location of those optimal strands generally depends on the loading rate. Optimal chains with a small number of cross-links were found to be almost as strong and tough as optimal chains with a large number of cross-links. Furthermore, optimality of chains with a small number of cross -links can be easily destroyed by adding cross-links at random. The present findings are relevant for the interpretation of single molecule force probe spectroscopy studies of the mechanical unfolding of "loadbearing" proteins, whose native topology often involves parallel strand arrangements similar to the optimal configurations identified in the study.

Topography of the free-energy landscape probed via mechanical unfolding of proteins

“…56 The fact that this model still captures the unfolding scenario observed in atomistic simulations supports the notion that native topology largely determines the mechanical unfolding mechanism. [72][73][74] From Fig. 4, the barrier separating the conformations I and II disappears at a force f Ϸ 1.2 h / ͑at T = 0.32 h ͒.…”

The resistance curve for subcritical cracks near the threshold

“…Once the forces have been determined, the time increment t toward the next event and the event itself can be computed using kinetic Monte-Carlo method (Voter 1986;Zhang et al 1990;Metiu et al 1992). Here, we closely follow the scheme used in Makarov et al (2001) and Eom et al (2005). Suppose that there are m bonds and n vacancies and the local time scale is set so that t 0 = 0.…”

Protein's native state stability in a chemically induced denaturation mechanism

“…To proceed with the generalization, we should notice that although denaturation can be triggered by a huge amount of different factors (Paliwal et al, 2004;Eom et al, 2005), one of the most studied cases in literature concerns the role of chemical agents like urea or GdnHCl in protein's native structure. As mentioned before, similar unfolding patterns have been observed experimentally throughout for different groups of proteins.…”