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

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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.

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DNA structures, lipid membranes, nicks, protein-mimicking, synthetic ion channel, tilt, DNA, Ion Channels, Lipid Bilayers, Nanostructures, Nanotechnology
Journal Title
Nano Lett
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American Chemical Society (ACS)
European Research Council (647144)
EPSRC (1948702)
Engineering and Physical Sciences Research Council (EP/S022953/1)
Winton Programme for the Physics of Sustainability EPSRC Scholarship (1948702). EPSRC Cambridge NanoDTC (EP/S022953/1) ERC consolidator grant (DesignerPores 647144) National Science Foundation USA (DMR-1827346) XSEDE allocation grant (MCA05S028) Leadership Resource Allocation (MCB20012)