Synthetic DNA-lipid conjugates combine a membrane localizing lipid component with a DNA head group. They are straightforward to prepare and characterize, with the DNA anchored to the lipid head group at either the 3’ or 5’ end. When two membranes displaying complimentary sequences come together and both are anchored at the 3’ or 5’ end, then the membranes are held separate by the length of the DNA hybrid (e.g. 8 nm for a 24mer). This can be used to create tethered vesicles on supported bilayers and vesicles or membrane bilayer patches can be directly attached and held away from a solid support. When one anchor is on the 3’ end while the other is 5’, hybridization forces the membranes together and they can fuse. This has been used to model vesicle fusion, both lipid mixing and content transfer. This strategy has been extended to enveloped viruses such as influenza and Zika where the DNA-lipid hybridization is a surrogate for viral receptor binding to its target. This provides a general platform for studying viral fusion when the native receptor is not known or difficult to work with and allows us to separate binding and fusion so that the mechanism of the latter can be studied directly.

Membrane architectures, vesicle and viral fusion using DNA-lipid conjugates

253rd National Meeting (2017)

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