Exclusion of Anchor-Matched Peptide Nucleic Acid from Liquid-Ordered Domains by Hybridization with Complementary Flavin-Labeled DNA.

Membrane-anchored proteins and their mimics, such as peptide nucleic acids (PNAs), are known to partition preferentially into either lipid raft/liquid-ordered (lo) domains or into non-raft/liquid-disordered (ld) domains, depending on their lipophilic anchors. Here, anchor-matched PNA was demonstrated to be excluded from the lo microdomains of giant unilamellar vesicles by hybridization with the complementary flavin-labeled DNA. As shown in control experiments using Alexa Fluor 488-labeled DNA, which showed that the preferential partitioning was the lo domain, the domain distribution of PNA was not only dependent on the lipophilic anchor but also on the structure of the hybridized DNA or PNA pair. In such systems, the main factors that influence changes in the domain selectivity of the probes are most likely to also be interactivity (i.e., steric bulkiness), hydrophilicity, and self-assembling ability. These findings may have the potential to contribute to the elucidation of membrane-active peptides, the method of their activation, and their applications in medicine such as antimicrobial use, especially with regard to their actions at the interface between the lo and ld domains in cells.