A quantitative assessment of the dynamic modification of lipid–DNA probes on live cell membranes

Synthetic lipid–DNA probes have recently attracted much attention for cell membrane analysis, transmembrane signal transduction, and regulating intercellular networks. These lipid–DNA probes can spontaneously insert onto plasma membranes simply after incubation. The highly precise and controllable DNA interactions have further allowed the programmable manipulation of these membrane-anchored functional probes. However, we still have quite limited understanding of how these lipid–DNA probes interact with cell membranes and also what parameters determine this process. In this study, we have systematically studied the dynamic process of cell membrane modification with a group of lipid–DNA probes. Our results indicated that the hydrophobicity of the lipid–DNA probes is strongly correlated with their membrane insertion and departure rates. Most cell membrane insertion stems from the monomeric form of probes, rather than the aggregates. Lipid–DNA probes can be removed from cell membranes through either endocytosis or direct outflow into the solution. As a result, long-term probe modifications on cell membranes can be realized in the presence of excess probes in the solution and/or endocytosis inhibitors. For the first time, we have successfully improved the membrane persistence of lipid–DNA probes to more than 24 h. Our quantitative data have dramatically improved our understanding of how lipid–DNA probes dynamically interact with cell membranes. These results can be further used to allow a broad range of applications of lipid–DNA probes for cell membrane analysis and regulation.