The cell membrane is a complex mixture of lipids, proteins,
and
other components. By forming dynamic lipid domains, different membrane
molecules can selectively interact with each other to control cell
signaling. Herein, we report several new types of lipid–DNA
conjugates, termed as “DNA zippers”, which can be used
to measure cell membrane dynamic interactions and the formation of
lipid domains. Dependent on the choice of lipid moieties, cholesterol-
and sphingomyelin-conjugated DNA zippers specifically locate in and
detect membrane lipid-ordered domains, while in contrast, a tocopherol–DNA
zipper can be applied for the selective imaging of lipid-disordered
phases. These versatile and programmable probes can be further engineered
into membrane competition assays to simultaneously detect multiple
types of membrane dynamic interactions. These DNA zipper probes can
be broadly used to study the correlation between lipid domains and
various cellular processes, such as the epithelial–mesenchymal
transition