Force-Dependent Folding and Unfolding Kinetics in DNA Hairpins Reveals Transition-State Displacements along a Single Pathway.
Biomolecules diffusively explore their energy landscape overcoming energy barriers via thermally activated processes to reach the biologically relevant conformation. Mechanically induced unfolding and folding reactions offer an excellent playground to feature these processes at the single-molecule level by monitoring changes in the molecular extension. Here we investigate two-state DNA hairpins designed to have the transition states at different locations. We use optical tweezers to characterize the force-dependent behavior of the kinetic barrier from nonequilibrium pulling experiments by using the continuous effective barrier approach (CEBA). We introduce the mechanical fragility and the molecular transition-state susceptibility, both useful quantities to characterize the response of the transition state to an applied force. Our results demonstrate the validity of the Leffler-Hammond postulate where the transition state approaches the folded state as force increases, implying monotonically decreasing fragility with force and a non-negative transition state susceptibility at all forces.
Small Biosystems Lab, Condensed Matter Physics Department, Universitat de Barcelona , Diagonal 647, 080028 Barcelona, Spain.
Anna
A
Alemany
Small Biosystems Lab, Condensed Matter Physics Department, Universitat de Barcelona , Diagonal 647, 080028 Barcelona, Spain.|Ciber-BBN, Networking Research Center of Bioengineering, Biomaterials and Nanomedicine, Instituto Carlos III , 28029 Madrid, Spain.
Felix
http://orcid.org/0000-0002-4869-5003
F
Ritort
D004247:DNA / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D052898:Optical Tweezers; D017510:Protein Folding; D013816:Thermodynamics
D004247:DNA