Controlling DNA adsorption and diffusion on lipid bilayers by the formation of lipid domains

We describe the influence of membrane heterogeneity on the adsorption and diffusion of DNA. Cellular membranes are believed to contain domains (lipid rafts) that influence processes ranging from signal transduction to the diffusion of membrane components. By analogy, we demonstrate that the formation of raft-like domains in supported lipid bilayers provides control over the adsorption and diffusion of DNA. The formation of bilayers from a mixture of the gel phase zwitterionic lipid 1,2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC) and the fluid phase cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) yielded coexisting DSPC-enriched and DOTAP-enriched phases. We demonstrated the ability to pattern the adsorption of DNA on the heterogeneous bilayers, with the adsorption being restricted to the DOTAP-enriched phase. We further demonstrated that the DSPC-enriched domains acted as obstacles to the lateral diffusion of adsorbed DNA. Fluorescence recovery after photobleaching (FRAP) analysis revealed that the diffusivity of the adsorbed DNA tracked that of the underlying lipid, although the lipid diffusivity changed by an order of magnitude with changes in bilayer composition. Fundamental insight into the adsorption and diffusion of DNA on heterogeneous surfaces may be useful for the design of novel techniques for the size-based separation of DNA.