Functional and Biomimetic DNA Nanostructures on Lipid Membranes

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Interface-Rich Materials and Assemblies

Functional and Biomimetic DNA Nanostructures on Lipid Membranes Na Wu, Feng Chen, Yue Zhao, Xu Yu, Jing Wei, and Yongxi Zhao Langmuir, Just Accepted Manuscript • DOI: 10.1021/acs.langmuir.8b01818 • Publication Date (Web): 25 Jul 2018 Downloaded from http://pubs.acs.org on July 28, 2018

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Functional and Biomimetic DNA Nanostructures on Lipid Membranes Na Wu, Feng Chen, Yue Zhao, Xu Yu, Jing Wei and Yongxi Zhao* Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an710049, P. R. China

ABSTRACT

Sophisticated and dynamic membrane-anchored DNA nanostructures were developed to mimic variety of membrane proteins, which play crucial roles on cellular functions. DNA biomimetic constructions bound on membranes are capable of modulating the morphologies, physical properties and functions of lipid membranes, via mobility on membranes and/or inherent architectural features. This inspired young field of DNA-lipid-based nanobiomimetic systems is on the foundation of DNA nanotechnology. In this review, we highlight key successes in the development of structural DNA nanotechnology and demonstrated some typical static and dynamic complex DNA nanostructures firstly. Then, we discussed the biophysical properties of lipid membranes. Primary approaches were shown to attach hydrophilic DNA to hydrophobic lipid membranes. With appropriate designs, membrane-floating DNA nanostructures assemble and disassemble on membranes, modulated by external stimulus. The aggregation of DNA nanostructures could influence the physical properties of lipid membranes. We also summarized

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artificial nanochannels made of DNA, analogous to transmembrane proteins. Transformations of DNA nanopores might be achieved under certain conditions and realized the transports of small molecules across membranes. Next, we focused on membrane-shaping functions of membraneanchored DNA nanostructures. Curvature of membrane is closely related to the rich diversity of cellular functions. Mimicking membrane-sculpting proteins, such as BAR family domains and SNARE proteins etc., DNA biomimetic nanostructures induced the transformations of lipid membranes and modulated membrane adhesion and membrane fusion processes. Although, recent studies in DNA nanostructure-lipid membrane biomimetic nanosystems have made great progresses, this field is still facing many challenges. In the future, the designs of more elaborated DNA architectures will be explored. Sophisticated dynamic DNA nanostructures inspired by natural membrane machines will be driven by the synergistic effect of multiple interactions, including hydrophobic force, electrostatic force and ligand-receptor interactions by chemical modifications on bases, to expand their applications in vivo from model membrane, cell membrane to karyotheca.

INTRODUCTION The fundamental cellular processes, like cell division, signal transduction, endocytosis and exocytosis, etc., are accompanied by the participation of cell membranes, which are formed via dynamic assemblies of phospholipid, membrane proteins and carbohydrates. The transport of signals/materials out of and into the cells is adjusted by the embedded variety of membrane proteins, containing peripheral and integral membrane proteins. It is crucial to deeply understand the interplay mechanisms of membrane proteins and lipid membranes. However, developing valuable proteins or acquiring novel protein structures via protein engineering is quite challenging.1 An innovative synthetic biology approach is required, which is based on the


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concept of redesigning and/or reconstituting biomimetic models to mimic protein-membrane related biological events. DNA, as a kind of self-assembled material, has the potential to expand the applications of synthetic biology with its biocompatibility and unique programmable properties.2-4 It should be pointed that DNA is much easier to be manipulated than proteins. After three decades of exploration in the field of structural DNA nanotechnology, DNA has become a powerful tool to construct both static and dynamic nanostructures with angstrom-scale precision and unprecedented complexity, which endows it with sufficient capacities to mimic proteins.1 DNA nanostructures are hydrophilic and negatively charged but lipid membranes are hydrophobic. This incompatibility could be conquered by conjugating lipophilic groups on oligonucleotide, which realized DNA-bound membrane system. In recent years, DNA nanostructure-lipid membrane systems were developed and investigated. A variety of complicated nanostructures were constructed with DNA, including that, flat architectures floating on bilayers mimic anchoring proteins;5-9 tubular structures are analogous to transmembrane proteins,10-13 like natural channels; curved structures with certain inherent curvatures imitate membrane sculpting proteins,14 and so on. Dynamic DNA nanostructures facilitate the exploration of behaviors of these DNA biomimetic architectures on lipid membrane. For example, the assembling/disassembling process of DNA bricks on membrane6,15 and the controllable channel entrance responding to local environment.12 On the other hand, the morphology, feature and physiological functions of lipid membrane could be influenced by the behaviors of DNA biomimetic structures.15,16 The related achievements will also be discussed. In this review, we will describe the elaborated DNA biomimetic architectures and discuss the recent representative DNA bionic nanostructures-lipid membrane models. We will focus on the


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dynamic aggregation behaviors of DNA nanostructures on lipid membranes, which were influenced by the physicochemical properties of membranes. Meanwhile, we will pay close attention to that the geometries and dynamic distributions of DNA bionic nanostructures will in turn affect the deformation and functions of lipid membranes. We further present the challenges and illustrate that more elaborated and stable DNA nanostructures are needed to be developed for the more extensive applications of lipid-DNA-based nanobiomimetic systems in vivo. DNA

NANOSTRUCTURES

WITH

SOPHISTICATED

AND

DYNAMIC

CONFORMATIONS After three decades of development, DNA nanotechnology is capacity of manufacturing unprecedented complex and dynamic nanostructures, which has greatly enriched the toolkit of synthetic biology. In 1982, inspired by a flying fish mural, Ned Seeman proposed an idea that using DNA Holliday Structure to build 3D periodic lattice to aid the crystallization of proteins,17 which opened the door of DNA nanotechnology. Later for a long time, DNA tiles assembly had always been a main developed strategy to construct variety of complex nanostructures.18,19 For example, Yin group developed a single-stranded DNA tile (SST) method (Figure 1A),20 which realized the arbitrary architectures and finite sizes.


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Figure 1. Static sophisticated DNA nanostructures. (A) Complex nanostructures assembled via single-stranded DNA tile (SST) strategy, which were designed using a molecular canvas.20 (B) Smiling face structure manufactured based on 2D DNA origami self-assembled strategy.21 (C) Multilayered 3D DNA origami structures constructed by packed helices with honeycomb lattices.25 (D) DNA nanoflask origami structure with complex curvature.27 However, DNA tiles assemble strategy is too intricate to be widespread applied. DNA origami technology was invented by Rothemund in 2006 (Figure 1B),21 which is a leap in the history of DNA nanotechnology. A commercially available long ssDNA (M13mp18 phage DNA), was folded into variety of 2D/3D predesigned patterns (rectangle, star, triangle and smile face etc.) by the fixation of hundreds of short staple strands. DNA origami technology renders DNA nanostructures broader applications due to its unprecedented sophisticated structures, great yield, unique addressability and simpler design philosophy. Open-source software, such as caDNAno,


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Tiamat etc.,22,23 significantly reduced the difficulty and effort in the design of complex 3D origami structures. Six 2D flat sheets were assembled to construct a box with a lid.24 Shih group provided a general design route for solid 3D origami structures by close-packing DNA helices into lattices in 3D space to form monolith, square nut, genie bottle and other shapes (Figure 1C).25 DNA origami with complex curvatures26 in 3D space was manufactured via adjusting the particular position and pattern of crossovers, such as a nanoflask, a square-toothed gears, etc. (Figure 1D).27 Mimicking membrane proteins requires not only sophisticated conformation, but also dynamic nature. DNA strand displacement was generously applied in adjusting the stiffness of compliant or hinge domain to produce dynamic reconfiguration of DNA nanostructures (Figure 2A-B).28-32 Castro and colleagues demonstrated DNA origami devices with an energy landscape defined by two stable states and actuated the transitions in states by DNA strand displacement or in the presence of molecular crowding agents (Figure 2A).32 Zhang et al. demonstrated a dynamic and reversible reconfiguration of DNA frame structure via a “fold-release-fold” strategy (Figure 2B).30 Simmel group developed a rotaxane structure composed of DNA origami subunits and switched the rotaxanes between a mobile and a fixed state with a fuel/anti-fuel mechanism.29 Song et al. demonstrated an artificial molecular array assembled from compliant DNA structural units to imitate information relay via conformational change cascades along DNA structure33 (Figure 2C). On the other hand, the diversity of DNA secondary structures rich the toolkit of the design of dynamic structures. DNA origami “pliers” translated between “open” and “close” states via DNA secondary structures, including i-motif, G-quadruplexes and ATP-aptamer etc.34,35 Wu et al. constructed trimer DNA origami tiles, which could be controllable assembled/disassembled with the presence/absence of cofactors by modifying responsive


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moieties at edges of the respective tiles.36,37 A linear origami structure turned to a bent shape by the change of pH values and this transition was reversible38 (Figure 2D). Shape-complementarity and short-ranged nucleobase stacking bonds could also be applied to help the construction of 3D dynamic DNA devices. Gerling et al. showed that dynamic conformations of DNA devices were adjusted by changing the cation concentration or temperature (Figure 2E).39 Reconfigurable complex nanostructures have shown greatly potential in mimicking proteins.

Figure 2. Dynamic DNA origami nanostructures. (A) A dynamic DNA devices can sense and respond to local environment with very high sensitivity, for example, it can measure depletion forces with a 100fN resolution via conformational transition under molecular crowding environment.32 (B) DNA strand displacement reactions were applied to induce a transformation from a simple DNA origami structure to a complex, quasifractal pattern.30 (C) A special information relay via the transformation of DNA arrays, initiated by specific trigger, and then propagated to adjacent sites and until to the entire array.33 (D) pH-stimulated reversible


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reconfiguration and structural isomerization of DNA origami trimer system.38 (E) A switch of DNA nanorobot between “closed” and “open” conformations via changing the surrounding temperature or the cation concentration.39 Organic dyes Atto550 and Atto647 were modified to enable a FRET-based readout of the transition between the two conformations. INTERACTION OF FUNCTIONAL DNA AND LIPID MEMBRANE Phospholipids are the major component of cell membranes, which consist of a hydrophobic hydrocarbon chain region - “tail” and a hydrophilic “head” containing a phosphate group. The amphipathy drives the hydrophobic tails to aggregate to form micelles or bilayer structures in water. The plasma membranes of cells contain lipid rafts, which are more ordered and tightly packed than the surrounding bilayers. Rafts contain 3 to 5-fold the amount of cholesterols, and enriched in sphingomyelin and saturated phospholipids. In model membrane systems, liquidordered (lo) phases, formed via mixing cholesterols and phospholipids, are generally served as rafts. The liquid-disordered (ld) phases are loosely packed, lack of cholesterol and enriched with unsaturated hydrocarbon chains.40 Different phases usually coexist in a mixture of lipids and play key roles in biological membrane functions. Hydrophilic, negatively charged DNA is mismatched with hydrophobic lipid bilayers. Hydrophobic groups could be introduced into DNA sequences by organic synthesis to regulate the hydrophobic and hydrophilic performance of the surface of DNA nanostructures. Liu group and Yan group used a frame-guided assembly (FGA) strategy to construct free-floating 2D amphiphilic assemblies and geometrically challenging 3D amphiphilic assemblies.41,42 The structure of assemblies is mainly determined by the inside geometry of the DNA scaffold and the distribution of leading hydrophobic groups modified on the surface of DNA nanostructures. Their work has the potential to construct more complex static/dynamic amphiphilic assemblies


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with sophisticated DNA scaffolds. Different types of hydrophobic groups were applied to enable the insertion of DNA strands/DNA nanostructures into lipid membranes. Porphyrin, as a kind of hydrophobic molecule, was covalently attached to DNA as a docking site to lipid membrane.43-46 Moreover porphyrin was multifunctional due to its electronic properties. Albinsson group reported a hexagonal DNA nanostructures functionalized with three Porphyrins nucleosides anchors at points could freely diffuse on lipid membrane and demonstrated the reversible process and a heat-induced self-repair mechanism of DNA nanostructures (Figure 3A).45 They also discussed the liposome porphyrin binding characteristics, such as orientation, anchor size and the number of anchoring points. The electron transfer here was studied by steady-state and timeresolved fluorescence and femtosecond transient absorption. Gopfrich et al. designed a duplex DNA with six porphyrin-tags to span lipid membrane to mimic ion channel.46 Incorporating electrophysiology measurements and molecular dynamic simulations, the microscopic conductance pathway was elucidated.

Figure 3. DNA nanostructures anchored to lipid membranes. (A) Schematic picture of a hexagonal DNA structure aligned onto lipid membrane via porphyrins with at least three attachment points.45 (B) Needle-like DNA origami structure with cholesteryl-ethylene glycol


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anchors, was served as a tool to study isotropic-nematic transition by observing the translocation on phase separated membranes.51 (C) A four-component DNA complex was with a double palmitoylated peptide nucleic acid (PNA-C16, partitioned to liquid-ordered domains), and a tocopherol anchor (partitioned to liquid-disordered domains). Enzymatic cleavage led to the disassembly of the complexes and then triggered the redistribution of the lipophilic nucleic acids into the respective domains.49 Lipid conjugation with DNA is another popular way to make an amphiphilic molecule to interact with lipid membrane. Cholesterol and tocopherol are the most commonly used lipophilic conjugates. The binding of cholesterol alone influences lipid membrane structure and dynamics to induce condensation of lipid, but cholesterol linked to tetraethylene glycol (chol-TEG) doesn’t display this property. In the mixtures of two fluid phases (lo & ld), chol-TEG-DNA conjugates equally distributed into both phases, while chol-DNA were partitioned into lo phase. In solidliquid coexisted phases, chol-TEG-DNA prefers to stay in ld phase.47,48 Schade et al. demonstrated a switchable partitioning of lipophilic DNA structures on ld/lo mixed phases. Enzymatic cleavage was used to induce the restoration of the initial distribution of the lipophilic nucleic acids into the respective domains, which offered a tool to study the molecular basis of controlled reorganization of membrane proteins/lipophilic nucleic acid nanostructures (Figure 3C).49 Czogalla demonstrated 3D nanorod on membrane with chol-TEG anchors, which is the first membrane-anchored DNA origami nanostructure.50 They studied the switchable domain partitioning and further investigated isotropic-nematic transition of DNA origami nanorods on membranes as the function of surface particle density (Figure 3B)51. The positions and numbers of decorated lipophilic anchors on DNA nanostructures greatly influence the binding behaviors with lipid membrane. It was proved that at least two chol-TEG moieties near the corners were


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necessary to the effective binding of large DNA nanostructures (DNA origami) on lipid membrane. Meanwhile, the increasing number of chol-TEG anchors lowered the freedom of DNA nanostructures on membrane.52 Sun et al. constructed an enzyme cascade system via incorporating the upstream glucose oxidase fixed on DNA origami raft and the downstream enzyme with ds-DNA anchored on the highly fluidic supported lipid bilayers (SLBs). The upstream enzyme is fixed on SLBs via 27 anchor strands decorated on origami raft, while the downstream enzyme is free diffused with only one lipophilic DNA anchor.53 The dynamic behaviors of proteins on 2D fluidic surfaces were controlled via different tethering mode to study their dynamic interactions. In fact, negatively charged unmodified DNA can also bind to zwitterionic lipid via electrostatic interactions in the presence of divalent cations, such as Mg2+ or Ca2+. Cations were thought to insert into the zwitterionic lipid to neutralize the negatively charge of lipid, resulting in a net positive charge.54 Concentration of cations would influence the binding behaviors of DNA nanostructures onto zwitterionic lipid. BEHAVIORS OF MEMBRANE-FLOATING DNA NANOSTRUCTURES Membrane protein clusters undergo complex conformational changes or aggregation behaviors on membranes to mediate the cell functions. These dynamic processes of proteins are affected by the surrounding environments and the properties of lipid membranes. The behaviors of DNA nanostructures on lipid membrane were studied to mimic dynamic membrane proteins. In order to mimic the membrane-cytoskeleton network structures, Suzuki et al. investigated the selfassembly of DNA origami tiles on a mica-supported zwitterionic lipid bilayer in the presence of divalent cations.7 Electrostatic force helped unmodified DNA origami tiles to absorb on SLBs to form large micrometer-sized lattices. The presence/absence of “blunt ends” affected the stacking


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manners, while high-speed atomic force microscopy (HSAFM) was used to record the dynamic processes, including fusion, reorganization and defect filling. Avakyan and co-workers considered the influence of lipid phases on the diffusion of DNA nanostructures on SLBs.55 They designed three-point star (3PS) DNA tiles modified/unmodified with cholesterol anchors to observe their respectively assemble behaviors on the fluid DOPC (1, 2-dioleoyl-sn-glycero-3phosphocholine) bilayer and the gel-like DPPC (1, 2-dipalmitoyl-sn-glycero-3-phosphocholine) bilayer. Meanwhile, the influence of π-stacking interactions on the dynamic morphologies was adequately considered via adding/removing blunt ended on the DNA tiles (Figure 4A). Environmental factors should be taken into account on the research of aggregation of DNA nanostructures on membranes. DNA strand hybridization or strand displacement is the most common manner. DNA origami blocks were polymerized into different superstructures on SLBs, following the addition of different connector DNA staples.56 Tan group reported the assembly and disassembly of DNA nanoprisms on cell-mimicking micrometer-scale giant membrane vesicles derived from living mammalian cells.57 The manipulation via dynamic strand hybridization and strand displacement, could serve as a new strategy for engineering artificial cell. They further constructed novel DNA probes, with different lipophilic anchors, to monitor the rapid membrane encounter events via transducing transient events to readable cumulative fluorescence signals.58 Of course other environmental factors were also studied. For example, Suzuki et al. introduced photo-responsive azobenzene-DNA moieties to the reversible assemble processes of hexagonal origami on lipid membrane (Figure 4B).59


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Figure 4. Dynamic diffusion and assembly/disassembly of DNA nanostructures on lipid membranes. (A) Long-range ordered distribution of blunt-ended DNA tiles on supported lipid bilayers (SLBs) based on the balance of π-stacking interactions at the ends, hydrophobic forces from the modified cholesterol anchors and electrostatic interactions between DNA tiles and SLBs.55 (B) High-speed atomic force microscopy recorded the dynamic assembly/disassembly processes of DNA origami nanostructures on SLBs, responding to UV/visible light irradiation.59 (C) Single-layered, cholesterol-modified DNA origami nanostructures were folded into bilayer structures due to the hydrophobic forces, and the bilayer nanostructures unfolded in the presence of lipid bilayer membranes.8 (D) A DNA nanorobot with molecular payloads responded to the cues on the surface of cell membranes to change their conformations to “open” states, then, the payloads were translated from nanorobots to cells.9 Except for the aggregation of proteins, the internal conformational changes of proteins also play a key role in physiological functions. Reconfiguration of DNA nanostructures has been achieved by various means. Simmel and co-workers constructed a “hydrophobic switching” DNA nanostructure,8 that was a twist-corrected single-layered DNA origami sheets modified with up to 35 cholesterol moieties on one face (Figure 4C). The high local concentration of cholesterols induced the sheet folded into bilayer formation along its long axis. Introducing the


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folded DNA bilayers into small unilamellar vesicles (SUVs) could promote the opening of bilayer structures, due to the favorable hydrophobic interactions between the cholesterol units and the lipid membranes. In the research reported by Douglas et al., structure-switching mechanism was applied in a DNA nanorobot system,9 which had the capacity to specifically target and attach to a cell membrane and transported the payloads to cell (Figure 4D). They designed a DNA barrel structure, consisting of two halves connected by four hinge regions. Aptamer-complement duplexes were served as “locks” appearing on two connected regions in the front of the barrel. When antigen “keys” existed on the cell surface, the barrel would attached to cell surface and revealing its molecular payload via “key”-induced switching from aptamercomplement duplexes to aptamer-target complexes. Several different logical “AND” gates were implemented to demonstrate their capacity in selective payloads transport. TRANS-MEMBRANE DNA NANOCHANNELS Trans-membrane proteins are the fundamental transport channels on cell membranes to regulate the exchange of ionic or molecular cargos between inside and outside of cells. In general, nanopores select cargos depending on the size, charge or other physicochemical properties. Beyond that, functional domains were served as stimulus-responsive molecular valves to control the transfer across biological bilayers. It is more difficult to realize artificial membrane penetration than construct membrane-floating structures. Higher energetic cost is required for DNA channels inserting into the hydrophobic lipid bilayers. The lipophilic anchors modified around the hydrophilic DNA channels, accompanied by membrane defects and electrical fields, break the energy barrier together. Using multiscale molecular dynamics (MD) simulations, Sansom and co-workers explored the stability and dynamics of an artificial DNA channel which


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inserted into a phospholipid bilayer via a ring of lipophilic anchors.60 Theoretical researches shed new light on the novel design of next-generation DNA nanopores. Recently, artificial synthetic membrane channels by self-assembled DNA nanostructures were developed.13,61 Simmel and co-workers created biomimetic transmembrane channel with DNA origami structure (Figure 5A).62 The structure was consisted of a hollow stem formed by six parallel DNA double helices, and a barrel-shaped cap around the stem. On the bottom of the cap, cholesterols were functionalized to anchor the structure in the membrane. TEM images confirmed that the structures indeed bound to lipid bilayer membranes. Single-channel electrophysiological measurements further proved the realization of membrane penetration. Single-molecule translocation experiments demonstrated that this synthetic channel could be used as sensing devices to discriminate single DNA molecules.

Figure 5. DNA nanostructures mimicking membrane channels. (A) Artificial nanochannel was consisted of a transmembrane-stem (red) and a barrel-shaped cap (white). Cholesterol anchors (orange) were modified on the bottom of cap to facilitate the attachment to lipid membrane.62 (B) A large-diameter, “T” shape DNA nanopore with stable electrical properties, allowed electrically


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driven translocation of ssDNA/dsDNA across it.63 (C) DNA nanochannel was capacity of selective transport of cargos cross lipid membrane by designing a DNA helix gate on the entrance.12 (D) The conformational reconfiguration of DNA nanochannel was driven by the charge neutralization. An expand state displayed “O” shape with the presence of Na+ , the addition of Mg2+ transported it into compact state with “11” shape and partially neutralizing with ethyl-phosphorothioate substitution rendered it partial compact state, exhibiting “8” shape.64 Except for cholesterol molecules, other chemical strategies were taken into account to facilitate the membrane-spanning. A neutral and hydrophobic outer ring comprised of phosphorothioateethyl groups was designed to overcome the energetic barrier toward membrane insertion.13 Burns et al. used only two porphyrin-based hydrophobic tags to realize the penetration of DNA nanostructure into the lipid bilayers.11 This very small number of anchors greatly simplified the chemical strategies for bilayer insertion of nanochannel. The fluorescent character of porphyrin made this channel structure easy to be observed under luminescence microscope. Kridhnan et al. created a DNA nanochannel (T pore) including a large central pore and a flat extramembranal part with lipophilic groups that facilitated a tighter attachment to the membrane (Figure 5B).63 Other than common hydrophobic anchors, streptavidin-biotin system was also applied to anchor the biotinylated channles to lipids. Dye influx experiments were implemented with T pore incorporated into a vesicle both in an outside-in and inside-out configuration. Dynamic DNA nanochannels were designed to control the transport of small molecular cargos across lipid membranes. Burns et al. designed a DNA nanochannel with a “gate” that was opened when binding of a ligand (Figure 5C).12 The “gate” was formed by a “lock” stand hybridizing to two docking sites on the entrance. A “key” would bond to the “lock” stand to remove it from entrance, and then opened the nanochannel. This system realized the sequence-specific and


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controlled release of small-molecule cargo from lipid vesicles. On the other hand, the transport of small organic molecules with a positively or negatively charged group would be obviously distinguished by this system. Liu et al. designed a computational-experimental approach to explore the underlying mechanism of DNA biomimetic molecular channels (Figure 5D).64 Charge neutralization-induced shape reconfigurable DNA nanotube was used here to demonstrate three typical states: expanded, compact and partially compact state. MD simulations were implemented under three different physiological conditions (Na+ and Mg2+ ions conditions or with DNA backbone modification). Incorporating with small angle X-ray scattering (SAXS) and Förster resonance energy transfer (FRET) characterization, the results showed that the nanochannel adopted a compact state by being neutralized by Mg2+ to form “II” shape; monovalent ions (Na+) switched it to the expansion state (“O” shape); whereas, ehylphosphorothioate substitution modified in DNA backbone kept it in partially compact state, which displaying “8” shape. This biomimetic system revealed the inherent relations between structure and function of biological channels and further gave cues for the design and applications of shape controllable DNA nanochannels. MEMBRANE TRANSFORMATION AND MEMBRANE FUSION INDUCED BY DNA NANOSTRUCTURES The complex conformational changes and behaviors of proteins, such as unfolding, aggregation on biological membranes etc., seriously influence the morphology, structure and functions of membranes.65,66 The curvatures of biological membranes have a very large span from cell membrane to organelle membrane, such as Golgi apparatus. The transformation of membranes is closely related to many physiological activities. For example, the change of curvatures plays a crucial role in the processes of membrane budding and membrane fusion.


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Membrane curvature not only relies on the membrane surface tension, but also is strongly affected by the specialized membrane-sculpting proteins such as clathrin, BAR and SNARE proteins.67-70 The intrinsic curvatures of these proteins or protein clusters induce the local deformation of membranes. Sophisticated DNA nanostructures have the capacity to mimic these specialized membranesculpting proteins to enable us to understand the relationship between clustering of proteins and the membrane deformation. Schwille group developed amphipathic DNA origami structures to mimic the membrane-sculpting proteins, such as the BAR family proteins.14,15 All BAR family proteins contains BAR domains, which induced different membrane behaviors according to respective mechanisms, such as F-BAR promoted membrane invaginations, I-BAR drove membrane protrusions and the stabilized planar membrane sheet was related to PinkBAR. To the latter protein, BAR domains aggregated on membrane via electrostatic and hydrophobic interactions to form tightly packed 2D scaffolds, to induce the deformation of membrane, at high surface densities. Authors designed 3D DNA origami platforms to mimic the flat sheet-like membrane-sculpting scaffold (PinkBAR) (Figure 6A).15 Cholesteryl-triethyleneglycol groups were modified on the bottom facet of the structure to facilitate its binding to membrane. Fluorescent molecules were decorated on the top facet to support fluorescence experiments. Sticky oligonucleotides were extended from the two opposing lateral sites. Complementary lateral strands were designed here to enable the oligomerization of origami DNA monoliths on membrane to lead to the membrane deformation of GUVs.


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Figure 6. Deformation of lipid membranes induced by DNA nanostructures mimicking membrane-sculpting proteins. (A) Flat amphipathic DNA origami structures were used as membrane-scaffolding tools. The extended “sticky” oligonucleotide overhangs enabled the two kind of DNA origami structures (green and cameo brown) assemble into ordered arrays on the membranes, which induced the deformation of lipid membranes.15 (B) DNA origami structures with variety of curvatures (origami L-linear, Q-quarter and H-half) developed to study their abilities to shape membranes, mimicking the architectures and functions of I-BAR, F-BAR and BAR/N-BAR domains, respectively.14 Of course, in-depth researches require designing and constructing curved DNA structures which more approaching the architectural features of scaffolding proteins. Following, Schwille and co-workers developed curved DNA origami structures with variety of curvatures to mimic BAR domain proteins to explore the properties of artificial scaffolds for sculpting lipid membrane (Figure 6B).14 BAR proteins exhibited different degrees of curvatures, for example, BAR/N-BAR dimers displayed high curvature, F-BAR dimers possessed moderate curvature and


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PinkBAR/I-BAR dimers were flat structures. In order to mimic the different BAR proteins, three shapes of DNA origami scaffolds were designed with different curvatures, respectively named origami H (semi-circle), origami Q (quarter-circle) and origami L (stick). Considering the membrane tension would affect the assembly behaviors of BAR domains, the osmolarity of the surrounding environment was increased to lower the membrane tension to test membrane deformation with the binding of different origami scaffolds. Results showed that moderately curved origami Q promoted the obvious tubular membrane deformation, but other curved origami scaffolds, H and L didn't exhibit remarkable inducement. The phenomenon was analyzed from the view of energy theory. They demonstrated that, in their DNA biomimetic system, curvature played a decision role, while, membrane affinity and surface density participated together to control the local membrane curvature. This work provided a novel strategy to explore the membrane shaping-related physiological phenomenon. Cell-cell adhesion and cell fusion can be adjusted by specific proteins. DNA nanostructures have the capacity to imitate and promote the processes. In earlier researches, anchored DNA was applied as linking groups for the programmable assembly of liposomes.71-73 The assembly was reversible and stimuli-responsive to environments. Shi et al. developed an engineered cell surface with polyvalent display of biomolecules (Figure 7A).74 Single stand initiator DNA was anchored on the surface of cell via chemical coupling, and then using DNA hybridization chain reaction to form branched DNA polymers on the cell surface. This strategy enabled the small number of exogenous biomolecules (initiator DNA) directly on the cell surface to generate polyvalent functionalization of cell. These polyvalent cells had higher efficiency in responding to microenvironment, comparing with monovalent ones, and were more efficient in developing


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microscale tissue constructs. Castro and co-workers developed a DNA origami nanoplatform as a membrane-bound breadboard to promote the programed adhesion of two living cells.75

Figure 7. Membrane adhesion and fusion mediated by DNA tethers/DNA nanostructures. (A) Polyvalent functionalization was realized on the surface of live cells via two-step reactions to promote the higher efficient recognizing of cells to microenvironment than that with monovalent functionalization.74 (B) DNA-lipid tethers brought two liposomes closer via DNA hybridization of 21 bps and controlled the separation distances between them, which significantly accelerated the SNARE-mediated membrane fusion.76 (C) DNA origami nanoring structure was designed to manufacture uniform-sized SUV, which bearing predetermined numbers of v-SNAREs (green) and DNA tethers (red). The system bypassed the rate-limiting docking step and allowed the directly observation of individual membrane-fusion events with only one pair SNAREs per vesicle.79 Cell fusion is driven by SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein. Xu et al. developed SNARE and DNA-mediated vesicle fusion system to


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explore the fusion mechanism (Figure 7B).76 In the fusion process, V-SNARE and t-SNARE proteins on separate membranes combined to a SNARE complex, which was seen as ratelimiting step, generally assumed in minutes. In order to promote the formation of SNARE complex, additional proteins-tethering factors were needed. DNA anchor was used to mimic the tethering factors in SNARE-mediated vesicle fusion. Here, DNA tethers played a role via control the distance between two opposed membranes to facilitate the fusion at maximum rate. However, the number of SNAREs was another influence factor in vesicle fusion. It was reported that two SNAREs was sufficient to promote fusion with slow rate, while, 15 pairs of SNAREs were required to maximize the rate. DNA nanoring structure was applied to control the limiting conditions, including the vesicle size,77,78 the orientation of the proteins and the number of SNARE per vesicle (Figure 7C).79 The system supported the directly observation of SNAREdependent fusion without the influence of rate-limiting step (formation of SNARE complex) and proved that 1-2 pairs of SNAREs were sufficient to drive fast vesicle fusion. This system had potential to be applied in more complicated protein systems with its orientation function and programmability. SUMMARY Sophisticated and dynamic DNA nanostructures have been constructed, with the development of structural DNA nanotechnology, which is the foundation of mimicking membrane proteins. Investigations of the interactions of bioinspired DNA nanostructures and lipid membranes have many applications in the fields of nanotechnology, bionics, cellular biology and synthetic biology. Hydrophobic anchors, cholesteryl, porphyrin etc., were modified on DNA nanostructures to help the insertion of hydrophilic, negatively DNA into lipid membrane. The integration of DNA nanostructures endowed plasma membrane variety of functions, such as


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constructing ordered assemblies of components on membrane, controlling molecule delivery or modulating cell-cell adhesion/fusion. Membrane mechanical properties could also be influenced by the anchored DNA nanostructures,16 some of which might be irreversible, for example, the induced membrane deformation. Ordered assemblies of DNA bricks on lipid membranes were observed, mimicking membranefloating proteins. The balance of hydrophobic forces, π-stacking interactions and electrostatic repulsion determined the aggregation state of membrane-floating DNA nanostructures.55 Besides, the phase property of lipid membranes is another principal factor need to be considered. DNA nanostructures with different lipophilic moieties were partitioned into diverse lipid domains.47,49,50 These factors might be used to rearrange and locate the reactants on membranes via engineered DNA platforms to trigger cell-scale chemical reactions or signaling cascade on the surface of cells. Furthermore, the biomimetic nanostructures with stiffness and flexibility could be used to improve the mechanical properties of lipid membranes. Tubular DNA nanochannels were inserted into lipid membranes and realized controllable transports of small molecules across membranes, mimicking channel proteins.10 In the future, it’s necessary to develop reconfigurable DNA nanopores, responding to the synergism of multiple environmental factors, which will shed light on the mechanical explorations of interplay between DNA nanopores and cell, while expand the applications of bionanoengineering on cellular biology. Curved DNA nanostructures were constructed to mimic membrane-sculpting proteins, including BAR family domains, clathrin and SNARE proteins etc.14,79 Curvature and transformation of lipid membranes are related to many cellular functions, such as clathrinmediated endocytosis. By mediating curvature, membrane affinity and surface density, it has been proved that curvature of protein-mimicking DNA structures is the decisive factor on


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transformation of membranes.14 Future researches on this filed will focus on the design and manufacture of more elaborated DNA nanostructures with different geometry, size and functional domains. Hydrophobic interaction, electrostatic force and molecular recognition might be considered as the main thrust to drive dynamic DNA nanostructures by introducing specific modifications on bases, such as ligands, responding to membrane receptors. Furthermore, more elaborated DNA architectures inspired by rich diversity of nature membrane machines, have potential to function with more complex lipid membrane, such as karyotheca. On the other hand, the in vivo applications require developing strategies to maintain the stability of DNA nanostructures under cellular environment and mitigate unwanted immune responses, which could be achieved by chemical modifications. The future developments in these fields will make DNA nanostructure-lipid membrane systems exciting in cellular biology and novel therapeutics.

AUTHOR INFORMATION Corresponding Author *E-mail: [email protected], Tel: 86-29-82668908. Notes The authors declare no competing financial interest. Biographies


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Na Wu received her Ph.D. in 2015 from Shanghai Institute of Applied Physics (SINAP), Chinese Academy of Sciences (CAS) under the supervision of Prof. Jun Hu. She worked as a postdoctoral researcher at the Department of Chemistry, Hebrew University of Jerusalem in Jerusalem, Israel under the supervisor of Prof. Itamar Willner. Currently, she is an associate professor in the School of Life Science and Technology, Xi’an Jiaotong University. Her current researches are focused on DNA nanotechnology and DNA molecular machine.

Yongxi Zhao received his M.S. and his Ph.D. from Xi’an Jiaotong University in 2005 and 2009, respectively. During his doctoral period, he moved to University of Washington, Seattle, under the joint educational project. Since 2009, he joined the faculty at Xi’an Jiaotong University and completed his postdoctoral research at Shanghai Institute of Applied Physics, Chinese Academy of Science from 2012 to 2014. He is now a professor of School of Life Science and Technology,


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Xi’an Jiaotong University. His current researches are focused on biosensors, bioimaging, and nanobiotechnology.

ACKNOWLEDGMENT This work was financially supported by the National Science Foundation of China (No. 31700861, No. 21475102 and No. 31671013), the Natural Science Foundation of Shanxi Province (S2018-JC-JQ-0037), the Fundamental Research Funds for the Central Universities and the “Young Talent Support Plan” of Xi’an Jiaotong University. REFERENCES (1) Howorka, S. Changing of the guard. Science 2016, 352, 890-891. (2) Czogalla, A.; Franquelim, Henri G.; Schwille, P. DNA Nanostructures on Membranes as Tools for Synthetic Biology. Biophys. J. 2016, 110, 1698-1707. (3)

Langecker, M.; Arnaut, V.; List, J.; Simmel, F. C. DNA Nanostructures Interacting with

Lipid Bilayer Membranes. Acc. Chem. Res. 2014, 47, 1807-1815. (4)

Lee, D. S.; Qian, H.; Tay, C. Y.; Leong, D. T. Cellular processing and destinies of

artificial DNA nanostructures. Chem. Soc. Rev. 2016, 45, 4199-4225. (5)

Johnson-Buck, A.; Jiang, S.; Yan, H.; Walter, N. G. DNA-Cholesterol Barges as

Programmable Membrane-Exploring Agents. ACS Nano 2014, 8, 5641-5649.


26

Page 27 of 37 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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(6)

Yang, Y.; Endo, M.; Hidaka, K.; Sugiyama, H. Photo-Controllable DNA Origami

Nanostructures Assembling into Predesigned Multiorientational Patterns. J. Am. Chem. Soc. 2012, 134, 20645-20653. (7)

Suzuki, Y.; Endo, M.; Sugiyama, H. Lipid-bilayer-assisted two-dimensional self-

assembly of DNA origami nanostructures. Nat. Commun. 2015, 6, 8052. (8)

List, D.-P. J.; Weber, M.; Simmel, F. C. Hydrophobic Actuation of a DNA Origami

Bilayer Structure. Angew. Chem., Int. Ed. 2014, 53, 4236-4239. (9)

Douglas, S. M.; Bachelet, I.; Church, G. M. A Logic-Gated Nanorobot for Targeted

Transport of Molecular Payloads. Science 2012, 335, 831-834. (10) Howorka, S. Building membrane nanopores. Nat. Nanotechnol. 2017, 12, 619-630. (11) Burns, J. R.; Gopfrich, K.; Wood, J. W. ; Thacker, V. V.; Stulz, E.; Keyser, U. F.; Howorka, S. Lipid-Bilayer-Spanning DNA Nanopores with a Bifunctional Porphyrin Anchor. Angew. Chem., Int. Ed. 2013, 52, 12069-12072. (12) Burns, J. R.; Seifert, A.; Fertig, N.; Howorka, S. A biomimetic DNA-based channel for the ligand-controlled transport of charged molecular cargo across a biological membrane. Nat. Nanotechnol. 2016, 11, 152-158. (13) Burns, J. R.; Stulz, E.; Howorka, S. Self-Assembled DNA Nanopores That Span Lipid Bilayers. Nano Lett. 2013, 13, 2351-2356. (14) Franquelim, H. G.; Khmelinskaia, A.; Sobczak, J.-P.; Dietz, H.; Schwille, P. Membrane sculpting by curved DNA origami scaffolds. Nat. Commun. 2018, 9, 811.


27

Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 28 of 37

(15) Aleksander, C.; J., K. D.; G., F. H.; Veselina, U.; Yixin, Z.; Ralf, S.; Petra, S. Amphipathic DNA Origami Nanoparticles to Scaffold and Deform Lipid Membrane Vesicles. Angew. Chem., Int. Ed. 2015, 54, 6501-6505. (16) Dohno, C.; Makishi, S.; Nakatani, K.; Contera, S. Amphiphilic DNA tiles for controlled insertion and 2D assembly on fluid lipid membranes: the effect on mechanical properties. Nanoscale 2017, 9, 3051-3058. (17) Seeman, N. C. Nucleic acid junctions and lattices. J. Theor. Biol. 1982, 99, 237-247. (18) Ke, Y.; Ong, L. L.; Sun, W.; Song, J.; Dong, M.; Shih, W. M.; Yin, P. DNA brick crystals with prescribed depths. Nat. Chem. 2014, 6, 994-1002. (19) Tian, C.; Li, X.; Liu, Z. Y.; Jiang, W.; Wang, G. S.; Mao, C. D. Directed Self‐Assembly of DNA Tiles into Complex Nanocages. Angew. Chem., Int. Ed. 2014, 53, 8041-8044. (20) Wei, B.; Dai, M.; Yin, P. Complex shapes self-assembled from single-stranded DNA tiles. Nature 2012, 485, 623-627. (21) Rothemund, P. W. K. Folding DNA to create nanoscale shapes and patterns. Nature 2006, 440, 297-302. (22) Douglas, S. M.; Marblestone, A. H.; Teerapittayanon, S.; Vazquez, A.; Church, G. M.; Shih, W. M. Rapid prototyping of 3D DNA-origami shapes with caDNAno. Nucleic Acids Res. 2009, 37, 5001-5006.


28

Page 29 of 37 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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(23) Ke, Y.; Douglas, S. M.; Liu, M.; Sharma, J.; Cheng, A.; Leung, A.; Liu, Y.; Shih, W. M.; Yan, H. Multilayer DNA Origami Packed on a Square Lattice. J. Am. Chem. Soc. 2009, 131, 15903-15908. (24) Andersen, E. S.; Dong, M.; Nielsen, M. M.; Jahn, K.; Subramani, R.; Mamdouh, W.; Golas, M. M.; Sander, B.; Stark, H.; Oliveira, C. L. P.; Pedersen, J. S.; Birkedal, V.; Besenbacher, F.; Gothelf, K. V.; Kjems, J. Self-assembly of a nanoscale DNA box with a controllable lid. Nature 2009, 459, 73-77. (25) Douglas, S. M.; Dietz, H.; Liedl, T.; Högberg, B.; Graf, F.; Shih, W. M. Self-assembly of DNA into nanoscale three-dimensional shapes. Nature 2009, 459, 414-419. (26) Dietz, H.; Douglas, S. M.; Shih, W. M. Folding DNA into Twisted and Curved Nanoscale Shapes. Science 2009, 325, 725-730. (27) Han, D.; Pal, S.; Nangreave, J.; Deng, Z.; Liu, Y.; Yan, H. DNA Origami with Complex Curvatures in Three-Dimensional Space. Science 2011, 332, 342-346. (28) Liu, M.; Fu, J.; Hejesen, C.; Yang, Y.; Woodbury, N. W.; Gothelf, K.; Liu, Y.; Yan, H. A DNA tweezer-actuated enzyme nanoreactor. Nat. Commun. 2013, 4, 2127. (29) List, J.; Falgenhauer, E.; Kopperger, E.; Pardatscher, G.; Simmel, F. C. Long-range movement of large mechanically interlocked DNA nanostructures. Nat. Commun. 2016, 7, 12414. (30) Zhang, F.; Nangreave, J.; Liu, Y.; Yan, H. Reconfigurable DNA Origami to Generate Quasifractal Patterns. Nano Lett. 2012, 12, 3290-3295.


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(31) Zhou, L.; Marras, A. E.; Su, H.-J.; Castro, C. E. Direct Design of an Energy Landscape with Bistable DNA Origami Mechanisms. Nano Lett. 2015, 15, 1815-1821. (32) Hudoba, M. W.; Luo, Y.; Zacharias, A.; Poirier, M. G.; Castro, C. E. Dynamic DNA Origami Device for Measuring Compressive Depletion Forces. ACS Nano 2017, 11, 6566-6573. (33) Song, J.; Li, Z.; Wang, P.; Meyer, T.; Mao, C.; Ke, Y. Reconfiguration of DNA molecular arrays driven by information relay. Science 2017, 357: eaan 3377. (34) Kuzuya, A.; Sakai, Y.; Yamazaki, T.; Xu, Y.; Komiyama, M. Nanomechanical DNA origami "single-molecule beacons" directly imaged by atomic force microscopy. Nat. Commun. 2011, 2, 449. (35) Walter, H.-K.; Bauer, J.; Steinmeyer, J.; Kuzuya, A.; Niemeyer, C. M.; Wagenknecht, H.A. “DNA Origami Traffic Lights” with a Split Aptamer Sensor for a Bicolor Fluorescence Readout. Nano Lett. 2017, 17, 2467-2472. (36) Wu, N.; Willner, I. DNAzyme-Controlled Cleavage of Dimer and Trimer Origami Tiles. Nano Lett. 2016, 16, 2867-2872. (37) Wu, N.; Willner, I. Programmed dissociation of dimer and trimer origami structures by aptamer-ligand complexes. Nanoscale 2017, 9, 1416-1422. (38) Wu, N.; Willner, I. pH-Stimulated Reconfiguration and Structural Isomerization of Origami Dimer and Trimer Systems. Nano Lett. 2016, 16, 6650-6655. (39) Gerling, T.; Wagenbauer, K. F.; Neuner, A. M.; Dietz, H. Dynamic DNA devices and assemblies formed by shape-complementary, non-base pairing 3D components. Science 2015, 347, 1446-1452.


30

Page 31 of 37 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

(40) Loew, M.; Springer, R.; Scolari, S.; Altenbrunn, F.; Seitz, O.; Liebscher, J.; Huster, D.; Herrmann, A.; Arbuzova, A. Lipid Domain Specific Recruitment of Lipophilic Nucleic Acids: A Key for Switchable Functionalization of Membranes. J. Am. Chem. Soc. 2010, 132, 1606616072. (41) Zhou, C.; Zhang, Y. Y.; Dong, Y. C.; Wu, F.; Wang, D. M.; Xin, L.; Liu, D. S. Precisely Controlled 2D Free-Floating Nanosheets of Amphiphilic Molecules through Frame-Guided Assembly. Adv. Mater. 2016, 28, 9819-9823. (42) Dong, Y. C.; Yang, Y. R.; Zhang, Y. Y.; Wang, D. M.; Wei, X. X.; Banerjee, S.; Liu, Y.; Yang, Z. Q.; Yan, H.; Liu, D. S. Cuboid Vesicles Formed by Frame-Guided Assembly on DNA Origami Scaffolds. Angew. Chem., Int. Ed. 2017, 56, 1586-1589. (43) Stulz, E. Nanoarchitectonics with Porphyrin Functionalized DNA. Acc. Chem. Res. 2017, 50, 823-831. (44) Woller, J. G.; Hannestad, J. K.; Albinsson, B. Self-Assembled Nanoscale DNAPorphyrin Complex for Artificial Light Harvesting. J. Am. Chem. Soc. 2013, 135, 2759-2768. (45) Borjesson, K.; Lundberg, E. P.; Woller, J. G.; Norden, B.; Albinsson B. Soft-Surface DNA Nanotechnology: DNA Constructs Anchored and Aligned to Lipid Membrane. Angew. Chem., Int. Ed. 2011, 50, 8312-8315. (46) Göpfrich, K.; Li, C.-Y.; Mames, I.; Bhamidimarri, S. P.; Ricci, M.; Yoo, J.; Mames, A.; Ohmann, A.; Winterhalter, M.; Stulz, E.; Aksimentiev, A.; Keyser, U. F. Ion Channels Made from a Single Membrane-Spanning DNA Duplex. Nano Lett. 2016, 16, 4665-4669.


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Page 32 of 37

(47) Beales, P. A.; Vanderlick, T. K. Partitioning of Membrane-Anchored DNA between Coexisting Lipid Phases. J. Phys. Chem. B 2009, 113, 13678-13686. (48) Bunge, A.; Loew, M.; Pescador, P.; Arbuzova, A.; Brodersen, N.; Kang, J.; Dähne, L.; Liebscher, J.; Herrmann, A.; Stengel, G.; Huster, D. Lipid Membranes Carrying Lipophilic Cholesterol-Based Oligonucleotides—Characterization and Application on Layer-by-Layer Coated Particles. J. Phys. Chem. B 2009, 113, 16425-16434. (49) Schade, M.; Knoll, A.; Vogel, A.; Seitz, O.; Liebscher, J.; Huster, D.; Herrmann, A.; Arbuzova, A. Remote Control of Lipophilic Nucleic Acids Domain Partitioning by DNA Hybridization and Enzymatic Cleavage. J. Am. Chem. Soc. 2012, 134, 20490-20497. (50) Czogalla, A.; Petrov, E. P.; Kauert, D. J.; Uzunova, V.; Zhang, Y.; Seidel, R.; Schwille, P. Switchable domain partitioning and diffusion of DNA origami rods on membranes. Faraday Discuss 2013, 161, 31-43. (51) Czogalla, A.; Kauert, D. J.; Seidel, R.; Schwille, P.; Petrov, E. P. DNA Origami Nanoneedles on Freestanding Lipid Membranes as a Tool To Observe Isotropic–Nematic Transition in Two Dimensions. Nano Lett. 2015, 15, 649-655. (52) Lundberg, E. P.; Feng, B.; Saeid Mohammadi, A.; Wilhelmsson, L. M.; Nordén, B. Controlling and Monitoring Orientation of DNA Nanoconstructs on Lipid Surfaces. Langmuir 2013, 29, 285-293. (53) Sun, L.; Gao, Y.; Xu, Y.; Chao, J.; Liu, H.; Wang, L.; Li, D.; Fan, C. Real-Time Imaging of Single-Molecule Enzyme Cascade Using a DNA Origami Raft. J. Am. Chem. Soc. 2017, 139, 17525-17532.


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(54) Gromelski, S.; Brezesinski, G. DNA Condensation and Interaction with Zwitterionic Phospholipids Mediated by Divalent Cations. Langmuir 2006, 22, 6293-6301. (55) Avakyan, N.; Conway, J. W.; Sleiman, H. F. Long-Range Ordering of Blunt-Ended DNA Tiles on Supported Lipid Bilayers. J. Am. Chem. Soc. 2017, 139, 12027-12034. (56) Kocabey, S.; Kempter, S.; List, J.; Xing, Y.; Bae, W.; Schiffels, D.; Shih, W. M.; Simmel, F. C.; Liedl, T. Membrane-Assisted Growth of DNA Origami Nanostructure Arrays. ACS Nano 2015, 9, 3530-3539. (57) Peng, R.; Wang, H.; Lyu, Y.; Xu, L.; Liu, H.; Kuai, H.; Liu, Q.; Tan, W. Facile Assembly/Disassembly of DNA Nanostructures Anchored on Cell-Mimicking Giant Vesicles. J. Am. Chem. Soc. 2017, 139, 12410-12413. (58) You, M.; Lyu, Y.; Han, D.; Qiu, L.; Liu, Q.; Chen, T.; Sam Wu, C.; Peng, L.; Zhang, L.; Bao, G.; Tan, W. DNA probes for monitoring dynamic and transient molecular encounters on live cell membranes. Nat. Nanotechnol. 2017, 12, 453-461. (59) Suzuki, Y.; Endo, M.; Yang, Y. Y.; Sugiyama, H. Dynamic Assembly/Disassembly Processes of Photoresponsive DNA Origami Nanostructures Directly Visualized on a Lipid Membrane Surface. J. Am. Chem. Soc. 2014, 136, 1714-1717. (60) Maingi, V.; Burns, J. R.; Uusitalo, J. J.; Howorka, S.; Marrink, S. J.; Sansom, M. S. P. Stability and dynamics of membrane-spanning DNA nanopores. Nat. Commun. 2017, 8, 14784. (61) Göpfrich, K.; Li, C.-Y.; Ricci, M.; Bhamidimarri, S. P.; Yoo, J.; Gyenes, B.; Ohmann, A.; Winterhalter, M.; Aksimentiev, A.; Keyser, U. F. Large-Conductance Transmembrane Porin Made from DNA Origami. ACS Nano 2016, 10, 8207-8214.


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(62) Langecker, M.; Arnaut, V.; Martin, T. G.; List, J.; Renner, S.; Mayer, M.; Dietz, H.; Simmel, F. C. Synthetic Lipid Membrane Channels Formed by Designed DNA Nanostructures. Science 2012, 338, 932-936. (63) Krishnan, S.; Ziegler, D.; Arnaut, V.; Martin, T. G.; Kapsner, K.; Henneberg, K.; Bausch, A. R.; Dietz, H.; Simmel, F. C. Molecular transport through large-diameter DNA nanopores. Nat. Commun. 2016, 7, 12787. (64) Liu, P.; Zhao, Y.; Liu, X. G.; Sun, J. X.; Xu, D. D.; Li, Y.; Li, Q.; Wang, L. H.; Yang, S. C.; Fan, C. H.; Lin, J. P. Charge Neutralization Drives the Shape Reconfiguration of DNA Nanotubes. Angew. Chem., Int. Ed. 2018, 57, 5418-5422. (65)

Pandey, A. P.; Haque, F.; Rochet, J.-C.; Hovis, J. S. α-Synuclein-Induced Tubule

Formation in Lipid Bilayers. J. Phys. Chem. B 2011 , 115, 5886-5893. (66) Baumgart, T.; Capraro, B. R.; Zhu, C.; Das, S. L. Thermodynamics and Mechanics of Membrane Curvature Generation and Sensing by Proteins and Lipids. Annu. Rev. Phys. Chem. 2011, 62, 483-506. (67) McMahon, H. T.; Gallop, J. L. Membrane curvature and mechanisms of dynamic cell membrane remodelling. Nature 2005, 438, 590-596. (68) McDonald, N. A.; Vander Kooi, C. W.; Ohi, M. D.; Gould, K. L. Oligomerization but Not Membrane Bending Underlies the Function of Certain F-BAR Proteins in Cell Motility and Cytokinesis. Dev. Cell 2015, 35, 725-736.


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(69) Saleem, M.; Morlot, S.; Hohendahl, A.; Manzi, J.; Lenz, M.; Roux, A. A balance between membrane elasticity and polymerization energy sets the shape of spherical clathrin coats. Nat. Commun. 2015, 6, 6249. (70) Gao, Y.; Zorman, S.; Gundersen, G.; Xi, Z.; Ma, L.; Sirinakis, G.; Rothman, J. E.; Zhang, Y. Single Reconstituted Neuronal SNARE Complexes Zipper in Three Distinct Stages. Science 2012, 337, 1340-1343. (71) Hernández-Ainsa, S.; Ricci, M.; Hilton, L.; Aviñó, A.; Eritja, R.; Keyser, U. F. Controlling the Reversible Assembly of Liposomes through a Multistimuli Responsive Anchored DNA. Nano Lett. 2016, 16, 4462-4466. (72) Dave, N.; Liu, J. Programmable Assembly of DNA-Functionalized Liposomes by DNA. ACS Nano 2011, 5, 1304-1312. (73) Beales, P. A.; Geerts, N.; Inampudi, K. K.; Shigematsu, H.; Wilson, C. J.; Vanderlick, T. K. Reversible Assembly of Stacked Membrane Nanodiscs with Reduced Dimensionality and Variable Periodicity. J. Am. Chem. Soc. 2013, 135, 3335-3338. (74) Shi, P.; Zhao, N.; Lai, J. P.; Coyne, J.; Gaddes, E. R.; Wang, Y. Polyvalent Display of Biomolecules on Live Cells. Angew. Chem., Int. Ed., 2018, 57, 1-6. (75) Akbari, E.; Mollica, M. Y.; Lucas, C. R.; Bushman, S. M.; Patton, R. A.; Shahhosseini, M.; Song, J. W.; Castro, C. E. Engineering Cell Surface Function with DNA Origami. Adv. Mater. 2017, 29, 1703632. (76) Xu, W. M.; Wang, J.; Rothman, J. E.; Pincet, F. Accelerating SNARE-Mediated Membrane Fusion by DNA-Lipid Tethers. Angew. Chem., Int. Ed. 2015, 54, 14388-14392.


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(77) Zhang, Z.; Yang, Y.; Pincet, F.; Llaguno, M. C.; Lin, C. Placing and shaping liposomes with reconfigurable DNA nanocages. Nat. Chem. 2017, 9, 653-659. (78) Yang, Y.; Wang, J.; Shigematsu, H.; Xu, W.; Shih, W. M.; Rothman, J. E.; Lin, C. Selfassembly of size-controlled liposomes on DNA nanotemplates. Nat. Chem. 2016, 8, 476-483. (79) Xu, W.; Nathwani, B.; Lin, C.; Wang, J.; Karatekin, E.; Pincet, F.; Shih, W.; Rothman, J. E. A Programmable DNA Origami Platform to Organize SNAREs for Membrane Fusion. J. Am. Chem. Soc. 2016, 138, 4439-4447.


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TOC:

Sophisticated DNA nanostructures attached on/inserted into lipid membranes mimicking membrane proteins and modulated the morphologies, physical properties and functions of lipid membranes via assemble/disassemble behaviors and/or inherent architectural features.


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Functional and Biomimetic DNA Nanostructures on Lipid Membranes

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