TY - JOUR
T1 - On the biophysics and kinetics of toehold-mediated DNA strand displacement
AU - Srinivas, Niranjan
AU - Ouldridge, Thomas E.
AU - Šulc, Petr
AU - Schaeffer, Joseph M.
AU - Yurke, Bernard
AU - Louis, Ard A.
AU - Doye, Jonathan P.K.
AU - Winfree, Erik
N1 - Funding Information:
National Science Foundation [CCF-0832824]; the Engineering and Physical Sciences Research Council [EP/I001352/1]; the Gordon and Betty Moore Foundation through the Caltech Programmable Molecular Technology Initiative; the Scatcherd European Trust; and University College, Oxford. Funding for open access charge: ‘Caltech Programmable Molecular Technology Initiative’, through the Gordon and Betty Moore Foundation.
PY - 2013/12
Y1 - 2013/12
N2 - Dynamic DNA nanotechnology often uses toeholdmediated strand displacement for controlling reaction kinetics. Although the dependence of strand displacement kinetics on toehold length has been experimentally characterized and phenomenologically modeled, detailed biophysical understanding has remained elusive. Here, we study strand displacement at multiple levels of detail, using an intuitive model of a random walk on a 1D energy landscape, a secondary structure kinetics model with single base-pair steps and a coarse-grained molecular model that incorporates 3D geometric and steric effects. Further, we experimentally investigate the thermodynamics of three-way branch migration. Two factors explain the dependence of strand displacement kinetics on toehold length: (i) the physical process by which a single step of branch migration occurs is significantly slower than the fraying of a single base pair and (ii) initiating branch migration incurs a thermodynamic penalty, not captured by state-of-the-art nearest neighbor models of DNA, due to the additional overhang it engenders at the junction. Our findings are consistent with previously measured or inferred rates for hybridization, fraying and branch migration, and they provide a biophysical explanation of strand displacement kinetics. Our work paves the way for accurate modeling of strand displacement cascades, which would facilitate the simulation and construction of more complex molecular systems.
AB - Dynamic DNA nanotechnology often uses toeholdmediated strand displacement for controlling reaction kinetics. Although the dependence of strand displacement kinetics on toehold length has been experimentally characterized and phenomenologically modeled, detailed biophysical understanding has remained elusive. Here, we study strand displacement at multiple levels of detail, using an intuitive model of a random walk on a 1D energy landscape, a secondary structure kinetics model with single base-pair steps and a coarse-grained molecular model that incorporates 3D geometric and steric effects. Further, we experimentally investigate the thermodynamics of three-way branch migration. Two factors explain the dependence of strand displacement kinetics on toehold length: (i) the physical process by which a single step of branch migration occurs is significantly slower than the fraying of a single base pair and (ii) initiating branch migration incurs a thermodynamic penalty, not captured by state-of-the-art nearest neighbor models of DNA, due to the additional overhang it engenders at the junction. Our findings are consistent with previously measured or inferred rates for hybridization, fraying and branch migration, and they provide a biophysical explanation of strand displacement kinetics. Our work paves the way for accurate modeling of strand displacement cascades, which would facilitate the simulation and construction of more complex molecular systems.
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U2 - 10.1093/nar/gkt801
DO - 10.1093/nar/gkt801
M3 - Article
C2 - 24019238
AN - SCOPUS:84887968813
SN - 0305-1048
VL - 41
SP - 10641
EP - 10658
JO - Nucleic acids research
JF - Nucleic acids research
IS - 22
ER -