Biological membranes are essential components of all living organisms, forming cell boundaries and facilitating crucial processes like membrane fusion.[1] However, our understanding of fusion is limited due to the lack of effective control tools. DNA nanotechnology has emerged as a promising solution, offering precise control over membrane morphology and interaction dynamics. Through the fabrication of DNA nanotools, we aim to control membrane fusion and investigate the interaction between DNA-lipid hybrid nanostructures. A mechanical DNA nanostructure that transitions from an open to a closed state,[2] facilitating fusion initiation of attached membrane vesicles is exploited. Using ensemble methods and direct stochastic optical reconstruction microscopy (dSTORM), we observed that vesicles exhibit wobbling around the defined anchoring site of DNA nanostructures. To further understand these interactions in 3D, we introduced a T-shaped DNA nanoprobe (DNP), exploring parameters like the number and position of cholesterol anchors. Ensemble methods and dSTORM revealed that DNP with a single lipid anchor can discriminate between differently sized vesicles, potentially aiding in the identification of diagnostically relevant exosomes.[3] This research advances DNA nanotechnology, paving the way for improved tools for membrane fusion control and the design of nanodevices for vesicle-based research, biosensing, and diagnostics.
[1] L. V. Chernomordik et al. 2008. Mechanics of membrane fusion. Nat. Struct. Mol. Biol.15, 675-683.
[2] F. N. Gür et al. 2021. Double- to single-strand transition induces forces and motion in DNA origami nanostructures. Adv. Mater. 33:2101986.
[3] H. Zhang et al. 2018. Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation. Nat. Cell Biol. 20, 332-343.