RESUMO
Cells use membrane proteins as gatekeepers to transport ions and molecules, catalyze reactions, relay signals, and interact with other cells. DNA nanostructures with lipidic anchors are promising as membrane protein mimics because of their high tunability. However, the design features specifying DNA nanostructures' functions in lipid membranes are yet to be fully understood. Here, we show that altering patterns of cholesterol units on a cubic DNA scaffold dramatically changes its interaction mode with lipid membranes. This results in simple design rules that allow a single DNA nanostructure to reproduce multiple membrane protein functions: peripheral anchoring, nanopore behavior, and conformational switching to reveal membrane-binding units. Strikingly, the DNA-cholesterol cubes constitute the first open-walled DNA nanopores, as only a quarter of their wall is made of DNA. This functional diversity can increase our fundamental understanding of membrane phenomena and result in sensing, drug delivery, and cell manipulation tools.
Assuntos
Materiais Biomiméticos/metabolismo , Colesterol/metabolismo , DNA/metabolismo , Nanoporos , Lipossomas Unilamelares/metabolismo , Materiais Biomiméticos/química , Colesterol/química , DNA/química , Proteínas de Membrana/química , Simulação de Dinâmica Molecular , Fosfatidilcolinas/química , Lipossomas Unilamelares/químicaRESUMO
DNA base-pairing is the central interaction in DNA assembly. However, this simple four-letter (A-T and G-C) language makes it difficult to create complex structures without using a large number of DNA strands of different sequences. Inspired by protein folding, we introduce hydrophobic interactions to expand the assembly language of DNA nanotechnology. To achieve this, DNA cages of different geometries are combined with sequence-defined polymers containing long alkyl and oligoethylene glycol repeat units. Anisotropic decoration of hydrophobic polymers on one face of the cage leads to hydrophobically driven formation of quantized aggregates of DNA cages, where polymer length determines the cage aggregation number. Hydrophobic chains decorated on both faces of the cage can undergo an intrascaffold "handshake" to generate DNA-micelle cages, which have increased structural stability and assembly cooperativity, and can encapsulate small molecules. The polymer sequence order can control the interaction between hydrophobic blocks, leading to unprecedented "doughnut-shaped" DNA cage-ring structures. We thus demonstrate that new structural and functional modes in DNA nanostructures can emerge from the synergy of two interactions, providing an attractive approach to develop protein-inspired assembly modules in DNA nanotechnology.
Assuntos
DNA/química , Modelos Moleculares , Nanoestruturas/química , Polímeros/química , Pareamento de Bases , Interações Hidrofóbicas e Hidrofílicas , Micelas , Nanotecnologia , TermodinâmicaRESUMO
Polymer self-assembly and DNA nanotechnology have both proved to be powerful nanoscale techniques. To date, most attempts to merge the fields have been limited to placing linear DNA segments within a polydisperse block copolymer. Here we show that, by using hydrophobic polymers of a precisely predetermined length conjugated to DNA strands, and addressable 3D DNA prisms, we are able to effect the formation of unprecedented monodisperse quantized superstructures. The structure and properties of larger micelles-of-prisms were probed in depth, revealing their ability to participate in controlled release of their constituent nanostructures, and template light-harvesting energy transfer cascades, mediated through both the addressability of DNA and the controlled aggregation of the polymers.
Assuntos
DNA/química , Nanoestruturas , Polímeros/química , MicelasRESUMO
Natural systems combine different supramolecular interactions in a hierarchical manner to build structures. In contrast, DNA nanotechnology relies almost exclusively on DNA base pairing for structure generation. Introducing other supramolecular interactions can expand the structural and functional range of DNA assemblies, but this requires an understanding of the interplay between these interactions. Here, an economic strategy to build DNA nanotubes functionalized with lipid-like polymers is reported. When these polymers are linked to the nanotube using a spacer, they fold inside to create a hydrophobic environment within the nanotube; the nanotube can encapsulate small molecules and conditionally release them when specific DNA strands are added, as monitored by single-molecule fluorescence microscopy. When the polymers are directly linked to the nanostructure without spacers, they interact intermolecularly to form a network of DNA bundles. This morphological switch can be directly observed using a strand displacement strategy. The two association modes result in different cellular uptake behavior. Nanotubes with internal hydrophobic association show dye-mediated mitochondrial colocalization inside cells; while the bundles disassemble into smaller polymer-coated structures that reduce the extent of nonspecific cellular uptake. This approach uncovers parameters to direct the hierarchical assembly of DNA nanostructures, and produces promising materials for targeted drug delivery.
Assuntos
Materiais Revestidos Biocompatíveis , DNA , Sistemas de Liberação de Medicamentos/métodos , Nanotubos/química , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , DNA/química , DNA/farmacologia , Células HeLa , Humanos , Interações Hidrofóbicas e Hidrofílicas , Nanotecnologia/métodosRESUMO
We report a micelle-templated method to enhance the reactivity of DNA with highly hydrophobic molecules. Lipids, chromophores and polymers can be conjugated to DNA in high yield and under mild conditions. This method expands the range of DNA-templated reactions for DNA-encoded libraries, oligonucleotide and drug delivery, nanopore mimetics and DNA nanotechnology.