Programmed folding of DNA origami structures through single-molecule force control.

Area of Science:

• Biophysics
• Nanotechnology
• Molecular Biology

Background:

• DNA origami design has advanced, but folding typically relies on thermal or chemical annealing.
• Existing methods can be slow and prone to kinetic traps, limiting programmability.

Purpose of the Study:

• To demonstrate a novel mechanical folding method for DNA origami structures.
• To explore a folding pathway inaccessible to thermal annealing.
• To enable faster and more programmable DNA nanostructure assembly.

Main Methods:

• Utilizing magnetic tweezers to apply mechanical tension to a single scaffold DNA, unfolding its secondary structures.
• Facilitating base pairing between the stretched scaffold DNA and staple strands.
• Quenching the force to complete nanostructure folding via staple strand displacement.

Main Results:

• Mechanical folding was achieved via a novel pathway, distinct from thermal annealing.
• Folding processes were well-defined and free from kinetic traps.
• Complete folding was achieved in under 10 minutes.
• Parallel folding of multiple DNA nanostructures was demonstrated through multiplexed manipulation.

Conclusions:

• Mechanical folding offers a rapid, programmable, and trap-free alternative to traditional DNA origami assembly.
• This method opens new avenues for controlling and designing DNA nanostructures.
• The findings suggest a future with enhanced programmability in DNA nanostructure folding pathways.