Complex cooperativity in DNA origami revealed via design-dependent defectivity.

Area of Science:

• Nanotechnology
• Biophysics
• Synthetic Biology

Background:

• DNA origami is a versatile platform for designing self-assembling nanostructures.
• Understanding the cooperative effects governing DNA origami assembly is crucial but challenging.
• The vast design space offers opportunities to investigate cooperativity.

Purpose of the Study:

• To probe and understand the cooperative effects in DNA origami assembly.
• To develop predictive metrics for assembly yield based on design variations.
• To identify design principles for optimizing DNA origami self-assembly.

Main Methods:

• Utilized design variations in DNA origami structures.
• Employed an accelerated assembly protocol to enhance sensitivity to design changes.
• Measured assembly yield and correlated it with structural features.

Main Results:

• Developed metrics linking thermal stability and fold cooperativity (beneficial short folds, detrimental long folds) to defectivity.
• Combined these metrics into a single parameter strongly correlating with assembly yield.
• Identified qualitative trends offering practical design insights.

Conclusions:

• A unified parameter can predict DNA origami assembly yield, aiding in design optimization.
• Understanding cooperativity is key to improving the predictability and efficiency of DNA origami assembly.
• This work provides a foundation for predictive modeling and best practices in DNA origami design.