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Liposomes with double-stranded DNA anchoring the bilayer to a hydrogel core.

ABSTRACT: Liposomes are important biomolecular nanostructures for handling membrane-associated molecules in the lab and delivering drugs in the clinic. In addition to their biomedical applications, they have been widely used as model cell membranes in biophysical studies. Here we present a liposome-based model membrane that mimics the attachment of membrane-resident molecules to the cytoskeleton. To facilitate this attachment, we have developed a lipid-based hybrid nanostructure in which the liposome bilayer membrane is covalently anchored to a biocompatible poly(ethylene) glycol (PEG) hydrogel core using short double-stranded DNA (dsDNA) linkers. The dsDNA linkers connect cholesterol groups that reside in the bilayer to vinyl groups that are incorporated in the cross-linked hydrogel backbone. Size exclusion chromatography (SEC) of intact and surfactant-treated nanoparticles confirms the formation of anchored hydrogel structures. Transmission electron microscopy (TEM) shows ~100 nm nanoparticles even after removal of unanchored phospholipids. The location of dsDNA groups at the hydrogel-bilayer interface is confirmed with a fluorescence assay. Using DNA as a linker between the bilayer and a hydrogel core allows for temperature-dependent release of the anchoring interaction, produces polymer nanogels with addressible hybridization sites on their surface, and provides a prototype structure for potential future oligonucleotide drug delivery applications.

SUBMITTER: Dayani Y

PROVIDER: S-EPMC3874235 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Liposomes with double-stranded DNA anchoring the bilayer to a hydrogel core.

Dayani Yasaman Y Malmstadt Noah N

Biomacromolecules 20131003 10

Liposomes are important biomolecular nanostructures for handling membrane-associated molecules in the lab and delivering drugs in the clinic. In addition to their biomedical applications, they have been widely used as model cell membranes in biophysical studies. Here we present a liposome-based model membrane that mimics the attachment of membrane-resident molecules to the cytoskeleton. To facilitate this attachment, we have developed a lipid-based hybrid nanostructure in which the liposome bila ...[more]

PMID: 24083513

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Project description:BackgroundTelomeres are protective cap structures at the ends of the linear eukaryotic chromosomes, which provide stability to the genome by shielding from degradation and chromosome fusions. The cap consists of telomere-specific proteins binding to the respective single- and double-stranded parts of the telomeric sequence. In addition to the nucleation of the chromatin structure the telomere-binding proteins are involved in the regulation of the telomere length. However, the telomeric sequences are highly diverged among yeast species. During the evolution this high rate of divergency presents a challenge for the sequence recognition of the telomere-binding proteins.ResultsWe found that the Saccharomyces castellii protein Rap1, a negative regulator of telomere length, binds a 12-mer minimal binding site (MBS) within the double-stranded telomeric DNA. The sequence specificity is dependent on the interaction with two 5 nucleotide motifs, having a 6 nucleotide centre-to-centre spacing. The isolated DNA-binding domain binds the same MBS and retains the same motif binding characteristics as the full-length Rap1 protein. However, it shows some deviations in the degree of sequence-specific dependence in some nucleotide positions. Intriguingly, the positions of most importance for the sequence-specific binding of the full-length Rap1 protein coincide with 3 of the 4 nucleotides utilized by the 3' overhang binding protein Cdc13. These nucleotides are very well conserved within the otherwise highly divergent telomeric sequences of yeasts.ConclusionsRap1 and Cdc13 are two very distinct types of DNA-binding proteins with highly separate functions. They interact with the double-stranded vs. the single-stranded telomeric DNA via significantly different types of DNA-binding domain structures. However, we show that they are dependent on coinciding nucleotide positions for their sequence-specific binding to telomeric sequences. Thus, we conclude that during the molecular evolution they act together to preserve a core sequence of the telomeric DNA.

Dataset Information

Liposomes with double-stranded DNA anchoring the bilayer to a hydrogel core.

Publications

Liposomes with double-stranded DNA anchoring the bilayer to a hydrogel core.

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