General Method for Modification of Liposomes for Encoded Assembly on Supported Bilayers

We recently reported a novel system shown schematically in Figure 1A in which intact lipid vesicles were assembled on a fluid-supported bilayer using oligonucleotide tethers.1 Functionalized oligonucleotides were covalently attached to the surface of pre-formed lipid vesicles by incorporating a small fraction of lipids with reactive headgroups during vesicle assembly. Vesicles display-ing oligonucleotides were then tethered to a fluid-supported bilayer displaying oligonucleotides of complementary sequence. These tethered vesicles retain their integrity and diffuse parallel to the plane of the supporting bilayer. Encoded arrays of tethered vesicles were created by displaying orthogonal sequences of oligonucleotides on a patterned bilayer surface.2,3 A major drawback of this method is the requirement for the inclusion of a reactive lipid during the vesicle assembly process. This may be incompatible with vesicles containing proteins (proteoliposomes), the ultimate target of th