Complex Donuts: Small Variations in DNA Sequence Dictate Pathway Complexity in DNA Nanotoroids

Area of Science:

• Biomaterials Science
• Nanotechnology
• Molecular Biology

Background:

• Natural biopolymer higher-order structure formation relies on sequence and chemistry.
• Nucleic acids assemble into nanostructures via base-pairing, but have limited chemical diversity.
• DNA amphiphiles use non-nucleosidic modifications for orthogonal interactions, forming diverse morphologies.

Purpose of the Study:

• To demonstrate that single-stranded DNA sequence, independent of base-pairing, can program DNA amphiphile self-assembled morphology.
• To investigate the formation of non-equilibrium DNA nanotoroids induced by small sequence variations.
• To explore stabilization methods and molecular dynamics of DNA nanotoroid formation.

Main Methods:

• Synthesizing DNA amphiphiles with specific single-stranded DNA sequences.
• Characterizing self-assembled morphologies using microscopy techniques.
• Utilizing molecular dynamics simulations to understand toroid formation mechanisms.
• Employing small molecule cross-linkers and co-assembly for stabilization.

Main Results:

• Precise DNA sequences, independent of base-pairing, dictate DNA amphiphile morphology.
• Small sequence variations trigger the formation of non-equilibrium DNA nanotoroids.
• Nanotoroids form via a competitive mechanism as on-pathway structures with toroid-selective sequences.
• Molecular dynamics confirm sequence-dependent toroid formation influenced by end-stacking structures.

Conclusions:

• Introduces a new class of DNA-based nanotoroid materials with sequence-controlled assembly.
• Demonstrates sequence-programmed self-assembly akin to protein folding.
• Highlights potential applications in cell delivery, nano-filtration, nanoreactors, and materials templation.