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


Change log
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.

Publication Date
2021-11-24
Online Publication Date
2021-11-12
Acceptance Date
2021-11-04
Keywords
DNA structures, lipid membranes, nicks, protein-mimicking, synthetic ion channel, tilt, DNA, Ion Channels, Lipid Bilayers, Nanostructures, Nanotechnology
Journal Title
Nano Lett
Journal ISSN
1530-6984
1530-6992
Volume Title
Publisher
American Chemical Society (ACS)
Sponsorship
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)