Structural DNA nanotechnology has emerged as a promising method for designing spontaneously inserting and fully-controllable synthetic ion channels. Earlier, we have shown that such membrane-spanning DNA-based channels can scramble lipids 10,000 faster than any known biological enzyme. However, both insertion efficiency and stability of existing DNA-based ion channels leave much room for improvement. Here, combining our MD simulations with the experiments performed by Keyser (Cambridge U., UK) lab, we demonstrated an approach to overcoming the unfavorable DNA-lipid interactions that hinder the formation of a stable transmembrane pore. In all-atom MD simulations, we observed that the DNA insertion-driving cholesterol modifications, when introduced at an end of a DNA strand, cause fraying of the terminal base pairs as the DNA nanostructure adopts its energy-minimum configuration in the membrane. The fraying of base pairs distorts nicked DNA constructs when embedded in a lipid bilayer. To avoid the undesirable distortion in the structure of DNA, we introduced a DNA nanostructures that do not have discontinuities (nicks) in their DNA backbones. This non-nicked DNA nanostructure leads to considerably more stable DNA-induced conductive pores and inserts into lipid membranes with a higher efficiency than the equivalent nicked constructs. Moreover, lack of nicks allows to design and maintain 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.