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Complex Donuts: Small Variations in DNA Sequence Dictate Pathway Complexity in DNA Nanotoroids
Muhammad Ghufran Rafique1, Yihao Wu1, Yutong Shi2
1Department of Chemistry, McGill University, 801 Sherbrooke St W, Montréal, QC, H3A 0B8, Canada.
Angewandte Chemie (International Ed. in English)
|June 14, 2025
Summary
Sequence-specific DNA amphiphiles self-assemble into novel nanotoroids. This discovery enables programmable nanostructure formation, expanding applications in materials science and nanomedicine.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Molecular Biology
Background:
- Natural biopolymers form higher-order structures via sequence and chemistry.
- Nucleic acids assemble into nanostructures using base-pairing, but have limited chemical diversity.
- DNA amphiphiles use non-nucleosidic modifications for orthogonal interactions and diverse morphologies.
Purpose of the Study:
- To investigate sequence-dependent self-assembly of DNA amphiphiles.
- To explore the formation of non-equilibrium nanostructures programmed by DNA sequence.
- To introduce a new class of DNA-based nanotoroid materials.
Main Methods:
- Synthesized DNA amphiphiles with specific single-stranded DNA sequences.
- Induce self-assembly and characterized resulting morphologies (spheres, fibers, nanosheets, nanotoroids).
- Utilized molecular dynamics simulations to understand toroid formation mechanisms.
Main Results:
- Precise single-stranded DNA sequences, independent of base-pairing, program DNA amphiphile morphology.
- Small sequence variations induce non-equilibrium DNA nanotoroids via a competitive mechanism.
- Nanotoroid formation depends on the end-p stacking unit structure.
Conclusions:
- DNA sequence alone can program self-assembled nanostructure morphology, similar to proteins.
- Introduced DNA nanotoroids as a new class of materials with sequence-controlled assembly.
- Potential applications include cell delivery, nano-filtration, nanoreactors, and materials templation.
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