Lipid Domain Specific Recruitment of Lipophilic Nucleic Acids: A Key for Switchable Functionalization of Membranes

Abstract

Lipid domains in mammalian plasma membranes serve as platforms for specific recruitment or separation of proteins involved in various functions. Here, we have applied this natural strategy of lateral separation to functionalize lipid membranes at micrometer scale in a switchable and reversible manner. Membrane-anchored peptide nucleic acid and DNA, differing in their lipophilic moieties, partition into different lipid domains in model and biological membranes. Separation was visualized by hybridization with the respective complementary fluorescently labeled DNA strands. Upon heating, domains vanished, and both lipophilic nucleic acid structures intermixed with each other. Reformation of the lipid domains by cooling led again to separation of membrane-anchored nucleic acids. By linking appropriate structures/functions to complementary strands, this approach offers a reversible tool for triggering interactions among the structures and for the arrangement of reactions and signaling cascades on biomimetic surfaces.

Terminal lipophilization of a unique DNA dodecamer by various nucleolipid headgroups: Their incorporation into artificial lipid bilayers and hydrodynamic properties

“…The studies described in this manuscript complement the research of various scientific groups whose work is focused on the formation of complex nanoarchitectures [33–34], the interaction of such nanostructures with lipid membranes [35–38], as well as the optimization of the in vivo delivery of lipophilic siRNA [10–12] (e.g., by DNA trafficking [7]).…”

Application of nucleic acid–lipid conjugates for the programmable organisation of liposomal modules

“…Loew et al demonstrated that palmitoylated peptide nucleic acids partition almost exclusively to liquid-ordered domains [66]. When combined with the L -partitioning tocopherol anchors discussed earlier, this allowed the construction of GUVs where each phase was encoded with a different DNA functionality.…”

“…3c) have also been used to stably anchor nucleic acids to membranes via two hydrocarbon chains [66].…”

Vesicles in Nature and the Laboratory: Elucidation of Their Biological Properties and Synthesis of Increasingly Complex Synthetic Vesicles

“…Vesicles exhibiting Janus-like morphology have also been constructed in aw ay that allowed the local confinement of DNA. [78,79] Inspired by how membrane proteins are targeted to raft domains through palmitoylation (i.e.t he post-translational addition of palmitic acid), Arbuzova and co-workers [79] were able to palmitoylate aDNA-recognizing peptide nucleic acid (PNA) with the aim of exclusively partitioning the PNA into the liquid-ordered domains of liquid-liquid phaseseparated giant unilamellar vesicles (GUVs). This strategy was highly effective and allowed the specific partitioning of lipophilic DNAa nd PNAm olecules into defined membrane environments to be combined with the reversible temper-ature-dependent intermixing of laterally separated membrane domains.…”