Entropy‐Driven Self‐Assembly of DNA Origami Isomers

Entropy can be an important factor to direct the self‐assembly of biomolecules into specific configurations, which requires repeatable and predictable design principles. Herein, a DNA origami system is presented, which folds into isomers with similar enthalpy but different conformational entropy due to loop formation of the scaffold, which is described quantitatively by an entropy model. It is demonstrated that the equilibrium distribution of a basic system consisting of two isomers can be tuned by changing the length, position, and number of scaffold loops, which is in good agreement with the model predictions. It is also shown that the folding pathway can be controlled kinetically through simple changes in the assembly protocol. Finally, a demonstration is done on how the equilibrium distribution of a more complicated system with six isomers can also be tuned in good agreement with model predictions. Overall, a new system and model for synthesizing nanoscale structures through predictable entropy‐driven self‐assembly of DNA origami is demonstrated. Given that the model is based on first principles, it is anticipated that the framework can be extended to the self‐assembly of other macromolecules such as proteins and RNA.