Abstract
DNA nanotechnology has emerged as a promising method for designing spontaneously inserting and fully controllable synthetic ion channels. However, both insertion efficiency and stability of existing DNA-based membrane channels leave much room for improvement. Here, we demonstrate an approach to overcoming the unfavorable DNA-lipid interactions that hinder the formation of a stable transmembrane pore. Our all-atom MD simulations and experiments show that the insertion-driving cholesterol modifications can cause fraying of terminal base pairs of nicked DNA constructs, distorting them when embedded in a lipid bilayer. Importantly, we show that DNA nanostructures with no backbone discontinuities form more stable conductive pores and insert into membranes with a higher efficiency than the equivalent nicked constructs. Moreover, lack of nicks allows design and maintenance of membrane-spanning helices in a tilted orientation within the lipid bilayer. Thus, reducing the conformational degrees of freedom of the DNA nanostructures enables better control over their function as synthetic ion channels.
Original language | English (US) |
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Pages (from-to) | 9789-9796 |
Number of pages | 8 |
Journal | Nano letters |
Volume | 21 |
Issue number | 22 |
DOIs | |
State | Published - Nov 24 2021 |
Keywords
- DNA structures
- lipid membranes
- nicks
- protein-mimicking
- synthetic ion channel
- tilt
ASJC Scopus subject areas
- Bioengineering
- General Chemistry
- General Materials Science
- Condensed Matter Physics
- Mechanical Engineering