Artificial water channels are synthetic molecules that aim to mimic structural and functional features of biological water channels (aquaporins). Here, we report on a cluster-forming organic nanoarchitecture, peptide-appended hybrid[4]arene (PAH[4]), as a new class of artificial water channels. Fluorescence experiments and simulations demonstrated that PAH[4]s can form clusters
Functionalization of quantum dots (QDs) with a single biomolecular tag using traditional approaches in bulk solution has met with limited success. DNA polyhedra consist of an internal void bounded by a well-defined three-dimensional structured surface. The void can house cargo and the surface can be functionalized with stoichiometric and spatial precision. Here, we show that monofunctionalized QDs can be achieved by encapsulating QDs inside DNA icosahedra and functionalizing the DNA shell with an endocytic ligand. We deployed the DNA-encapsulated QDs for real time imaging of three different endocytic ligands - folic acid, galectin-3 (Gal3) and the Shiga toxin B-subunit (STxB). Single particle tracking of Gal3 or STxB-functionalized, QD-loaded DNA icosahedra allows us to monitor compartmental dynamics along endocytic pathways. These DNA-encapsulated QDs that bear a unique stoichiometry of endocytic ligands represent a new class of molecular probes for quantitative imaging of endocytic receptor dynamics.
DNA nanotechnology allows for the design of programmable DNA-built nanodevices which controllably interact with biological membranes and even mimic the function of natural membrane proteins. Hydrophobic modifications, covalently linked to the DNA, are essential for targeted interfacing of DNA nanostructures with lipid membranes. However, these hydrophobic tags typically induce undesired aggregation eliminating structural control, the primary advantage of DNA nanotechnology. Here, we study the aggregation of cholesterol-modified DNA nanostructures using a combined approach of non-denaturing polyacrylamide gel electrophoresis, dynamic light scattering, confocal microscopy and atomistic molecular dynamics simulations. We show that the aggregation of cholesterol-tagged ssDNA is sequence-dependent, while for assembled DNA constructs, the number and position of the cholesterol tags are the dominating factors. Molecular dynamics simulations of cholesterol-modified ssDNA reveal that the nucleotides wrap around the hydrophobic moiety, shielding it from the environment. Utilizing this behavior, we demonstrate experimentally that the aggregation of cholesterol-modified DNA nanostructures can be controlled by the length of ssDNA overhangs positioned adjacent to the cholesterol. Our easy-to-implement method for tuning cholesterol-mediated aggregation allows for increased control and a closer structure–function relationship of membrane-interfacing DNA constructs — a fundamental prerequisite for employing DNA nanodevices in research and biomedicine.
Reported herein is a series of pore‐containing polymeric nanotubes based on a hydrogen‐bonded hydrazide backbone. Nanotubes of suitable lengths, possessing a hollow cavity of about a 6.5 Å diameter, mediate highly efficient transport of diverse types of anions, rather than cations, across lipid membranes. The reported polymer channel, having an average molecular weight of 18.2 kDa and 3.6 nm in helical height, exhibits the highest anion‐transport activities for iodide (EC50=0.042 μm or 0.028 mol % relative to lipid), whcih is transported 10 times more efficiently than chlorides (EC50=0.47 μm). Notably, even in cholesterol‐rich environment, iodide transport activity remains high with an EC50 of 0.37 μm. Molecular dynamics simulation studies confirm that the channel is highly selective for anions and that such anion selectivity arises from a positive electrostatic potential of the central lumen rendered by the interior‐pointing methyl groups.
The outstanding capacity of aquaporins (AQPs) for mediating highly selective superfast water transport 1-7 has inspired recent development of supramolecular monovalent ion-excluding artificial water channels (AWCs). AWC-based bioinspired membranes are proposed for desalination, water purification, and other separations applications [8][9][10][11][12][13][14][15][16][17][18] . While some recent progress has been made in synthesizing AWCs that approach the water permeability and ion selectivity of AQPs, a hallmark feature of AQPshigh water transport while excluding protons has not been reproduced. We report on a class of biomimetic, helically folded pore-forming polymeric foldamers, that can serve as long sought-after highly selective ultrafast water-conducting channels exceeding those of AQPs (1.1 × 10 10 H2O molecules/s for AQP1 7 ), with high water over monovalent ion transport selectivity (~10 8 water molecules over Clion) conferred by the modularly tunable hydrophobicity of the interior pore surface. The best-performing AWC reported here delivers water transport at an exceptionally high rate, 2.5 times that of AQP1, while concurrently rejecting salts (NaCl and KCl) and even protons.
The interplay between nucleic acids and lipids underpins several key processes in molecular biology, synthetic biotechnology, vaccine technology, and nanomedicine. These interactions are often electrostatic in nature, and much of their rich phenomenology remains unexplored in view of the chemical diversity of lipids, the heterogeneity of their phases, and the broad range of relevant solvent conditions. Here we unravel the electrostatic interactions between zwitterionic lipid membranes and DNA nanostructures in the presence of physiologically relevant cations, with the purpose of identifying new routes to program DNA–lipid complexation and membrane-active nanodevices. We demonstrate that this interplay is influenced by both the phase of the lipid membranes and the valency of the ions and observe divalent cation bridging between nucleic acids and gel-phase bilayers. Furthermore, even in the presence of hydrophobic modifications on the DNA, we find that cations are still required to enable DNA adhesion to liquid-phase membranes. We show that the latter mechanism can be exploited to control the degree of attachment of cholesterol-modified DNA nanostructures by modifying their overall hydrophobicity and charge. Besides their biological relevance, the interaction mechanisms we explored hold great practical potential in the design of biomimetic nanodevices, as we show by constructing an ion-regulated DNA-based synthetic enzyme.
We present an atomistic model of pillared DNA nanotubes (DNTs) and their elastic properties which will facilitate further studies of these nanotubes in several important nanotechnological and biological applications. In particular, we introduce a computational design to create an atomistic model of a 6-helix DNT (6HB) along with its two variants, 6HB flanked symmetrically by two double helical DNA pillars (6HB+2) and 6HB flanked symmetrically by three double helical DNA pillars (6HB+3). Analysis of 200 ns all-atom simulation trajectories in the presence of explicit water and ions shows that these structures are stable and well behaved in all three geometries. Hydrogen bonding is well maintained for all variants of 6HB DNTs. We calculate the persistence length of these nanotubes from their equilibrium bend angle distributions. The values of persistence length are ~10 μm, which is 2 orders of magnitude larger than that of dsDNA. We also find a gradual increase of persistence length with an increasing number of pillars, in quantitative agreement with previous experimental findings. To have a quantitative understanding of the stretch modulus of these tubes we carried out nonequilibrium Steered Molecular Dynamics (SMD). The linear part of the force extension plot gives stretch modulus in the range of 6500 pN for 6HB without pillars which increases to 11,000 pN for tubes with three pillars. The values of the stretch modulus calculated from contour length distributions obtained from equilibrium MD simulations are similar to those obtained from nonequilibrium SMD simulations. The addition of pillars makes these DNTs very rigid. KEYWORDS:DNA nanotubes, molecular dynamics, persistence length, Holliday junctions. 3DNA is an excellent material of choice for the precise organization of chemical species on the nanoscale. [1][2][3][4] The specific base pairing rules that enable DNA to function as a biological information carrier also facilitate the construction of DNA assemblies in a programmable manner. The interstrand interactions and sticky ended cohesion of DNA molecules provide a scaffold for the synthesis of branched DNA nanostructures with excellent precision. 5 In the past few decades, various novel nanostructures such as cubes, 6 tetrahedra, 7 truncated octahedra, 8 icosahedra, 9 smiley faces, two dimensional arrays 10-13 and nanotubes [14][15][16][17] have been synthesized using the versatile DNA molecule. Nanomechanical devices have also been constructed using DNA motifs, extending their potential application to DNA nanorobotics. [18][19][20] The introduction of DNA origami 21 has significantly accelerated the synthesis of various DNA nanostructures.Looking forward to the application of DNA nanotubes (DNTs) in cellular drug delivery, researchers are investigating their self-assembly and interaction with lipid membranes. 22, 23 The development of techniques such as DNA origami along with computational tools such as caDNAno 24 and 3DNA 25 has made their fabrication and analysis fast and efficient. With a...
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