Membrane Activity of a DNA-Based Ion Channel Depends on the Stability of Its Double-Stranded Structure.
American Chemical Society (ACS)
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Morzy, D., Joshi, H., Sandler, S. E., Aksimentiev, A., & Keyser, U. F. (2021). Membrane Activity of a DNA-Based Ion Channel Depends on the Stability of Its Double-Stranded Structure.. Nano Lett https://doi.org/10.1021/acs.nanolett.1c03791
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.
DNA structures, lipid membranes, nicks, protein-mimicking, synthetic ion channel, tilt
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)
European Research Council (647144)
Engineering and Physical Sciences Research Council (EP/S022953/1)
External DOI: https://doi.org/10.1021/acs.nanolett.1c03791
This record's URL: https://www.repository.cam.ac.uk/handle/1810/330458
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