Membrane Activity of a DNA-Based Ion Channel Depends on the Stability of Its Double-Stranded Structure

Diana Morzy, Himanshu Joshi, Sarah E. Sandler, Aleksei Aksimentiev, Ulrich F. Keyser

Research output: Contribution to journalArticlepeer-review


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 languageEnglish (US)
Pages (from-to)9789-9796
Number of pages8
JournalNano letters
Issue number22
StatePublished - Nov 24 2021


  • 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


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