Controlling the Rate and the Level of Interleaflet Lipid Transport with Switchable DNA Nanostructure

Abstract

The field of synthetic transmembrane structures encounters challenges in introducing complex protein-inspired features that allow them to exhibit control over lipid bilayer, and simultaneously tune their activity in response to external stimuli. Using DNA as a building material, we engineer structures that mimic the functionality of proteins, and establish control over model membranes under investigation. [1-2] We have developed a minimalist - yet highly functional - nucleic acid construct that self-assembles in a solution and inserts into lipid membranes, mimicking the way proteins model lipids surrounding them. Taking into consideration the interactions between DNA, its hydrophobic modifications and lipids, we successfully changed the lipid symmetry of the bilayer, controlling both the rate and level of these changes. Furthermore, we report cation-dependent activity of these structures, making them responsive to the chemical changes in the environment in a reversible manner. [3] Presented constructs show how powerfully and efficiently a simple design can mimic naturally occurring molecules; DNA structures lay a solid foundation for further development of more complex and sophisticated platforms. [1] A. Ohmann et al. Nature Communications, 9:2426, 2018. [2] K. Göpfrich et al. Nano Letters, 16(7):4665-4669, 2016 [3] D. Sobota et al. under preparation