Modelling DNA origami self-assembly at the domain level.

Area of Science:

• Biophysics
• Nanotechnology
• Molecular Biology

Background:

• DNA origami enables precise nanoscale construction.
• Understanding the kinetics of DNA origami folding is crucial for predictable assembly.
• Existing models often struggle with the complex geometry and thermodynamic calculations.

Purpose of the Study:

• To develop a kinetic modelling framework for DNA origami folding at the DNA domain level.
• To account for thermodynamic factors like coaxial stacking and entropic costs in staple binding.
• To provide a model that accurately reproduces experimental observations and can be extended to various origami structures.

Main Methods:

• Developed an explicit kinetic model for DNA origami folding.
• Incorporated free-energy changes based on staple sequence, coaxial stacking, and entropic constraints.
• Addressed the geometric complexity of scaffold constraints for planar origami.
• Introduced cooperative interactions between staples through coaxial stacking and entropic terms.

Main Results:

• Predicted sharp assembly transitions with hysteresis, aligning with experimental data.
• Successfully reproduced experimental outcomes related to staple concentration, cooling rates, and staple absence.
• Demonstrated the model's ability to capture cooperative interactions influencing folding pathways.
• Validated the model's predictions against known experimental observations in DNA origami.

Conclusions:

• The developed kinetic model provides a robust framework for studying DNA origami folding.
• The model accurately captures the influence of thermodynamic and kinetic factors on assembly.
• A simplified methodology is presented, expanding applicability to non-planar DNA origami systems.