Evidence of disorder in biological molecules from single molecule pulling experiments

Abstract

Heterogeneity in biological molecules, resulting in molecule-to-molecule variations in their dynamics and function, is an emerging theme. To elucidate the consequences of heterogeneous behavior at the single molecule level, we propose an exactly solvable model in which the unfolding rate due to mechanical force depends parametrically on an auxiliary variable representing an entropy barrier arising from fluctuations in internal dynamics. When the rate of fluctuations, a measure of dynamical disorder, is comparable to or smaller than the rate of force-induced unbinding, we show that there are two experimentally observable consequences: non-exponential survival probability at constant force, and a heavy-tailed rupture force distribution at constant loading rate. By fitting our analytical expressions to data from single molecule pulling experiments on proteins and DNA, we quantify the extent of disorder. We show that only by analyzing data over a wide range of forces and loading rates can the role of disorder due to internal dynamics be quantitatively assessed.

10 pages, 3 figures, Phys. Rev. Lett. (in press)

References in corpus (5)

• Forced-unfolding and force-quench refolding of RNA hairpins
• Hidden Complexity in the Isomerization Dynamics of Holliday Junctions
• Measuring the energy landscape roughness and the transition state location of biomolecules using single molecule mechanical unfolding experiments
• Force-clamp analysis techniques reveal stretched exponential unfolding kinetics in ubiquitin
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Cited by in corpus (8)

• Directly measuring single molecule heterogeneity using force spectroscopy
• Contact statistics highlight distinct organizing principles of proteins and RNA
• Direct and simultaneous measurement of the stiffness and internal friction of a single folded protein
• Understanding the dependence on the pulling speed of the unfolding pathway of proteins
• Dynamic coarse-graining fills the gap between atomistic simulations and experimental investigations of mechanical unfolding
• Decoding Single Molecule Time Traces with Dynamic Disorder
• Ubiquitous Dynamical Time Asymmetry in Measurements on Materials and Biological Systems
• Molecular Mechanism of Transition from Catch-Bond to Slip-Bond in Fibrin