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Jun 2024 • Molecular Cancer Therapeutics

Abstract PR008: Targeting mechanisms of dosage compensation to selectively kill aneuploid cancer cells

Hajime Okada, Eran Sdeor, Miriam Karmon, Erez Levanon, Uri Ben-David

Aneuploidy is an abnormal chromosome composition and a general hallmark of human cancer. Aneuploidy causes detrimental cellular stresses, but cancer cells evolve to cope with these stresses. Consequently, targeting such mitigation mechanisms is a promising potential therapeutic strategy. As an abnormal dosage of gene products from altered chromosomes can cause RNA and proteotoxic stress, dosage compensation (DC) of imbalanced gene products was reported to mitigate these stresses in aneuploid cells. However, the mechanisms that regulate DC remain elusive. To address these mechanisms, we focused on the role(s) of stress granules (SGs) and RNA binding proteins (RBPs) in aneuploid cancer cells. Our recent study revealed that aneuploid cancer cells preferentially depend on RNA and protein metabolism, and need to attenuate translation in order to cope with proteotoxic stress (Ippolito & …

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Jun 2024 • Quantum Technologies 2024, PC129930R, 2024

Entanglement-preserving measurement of the Bell parameter on a single entangled pair

Francesco Atzori, Salvatore Virzì, Enrico Rebufello, Alessio Avella, Fabrizio Piacentini, Rudi Lussana, Iris Cusini, Francesco Madonini, Federica Villa, Marco Gramegna, Eliahu Cohen, Ivo Pietro Degiovanni, Marco Genovese

Bell tests serve as a fundamental tool in both quantum technologies and quantum foundations investigation. The traditional Bell test framework involves the use of projective measurements, which, because of the wavefunction collapse and the Heisenberg uncertainty principle, do not allow for the full estimation of the Bell parameter from each entangled pair. In this work, we propose a novel weak-measurement-based scheme enabling the complete estimation of the entire Bell parameter from each entangled pair. Moreover, this approach prevents the collapse of the quantum state wavefunction, thereby preserving the entanglement within it. Our results, showing a 6 standard deviations violation of the Bell inequality tested, are obtained while leaving the entanglement within the photon pair almost unaltered after the weak measurement scheme (as demonstrated by our quantum tomographic reconstructions), allowing …

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Jun 2024 • Specialty Optical Fibres VIII, PC130010C, 2024

Opto-mechanical sensors of media outside the fiber

Avi Zadok

A new concept for the sensing of media outside the cladding boundary of standard unmodified fibers will be presented. Light in the single optical mode is used to stimulate mechanical modes of the entire cladding cross-section. The boundary conditions for the oscillations of the mechanical modes are modified by surrounding substances: the outward dissipation of mechanical waves manifests in faster decay rates. The process is monitored through photoelastic scattering of additional optical probe waves. Point-measurements, spatially distributed analysis, and monitoring of coating layers will be presented.

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Jun 2024 • Genes & Immunity

Resolving haplotype variation and complex genetic architecture in the human immunoglobulin kappa chain locus in individuals of diverse ancestry

Eric Engelbrecht, Oscar L Rodriguez, Kaitlyn Shields, Steven Schultze, David Tieri, Uddalok Jana, Gur Yaari, William D Lees, Melissa L Smith, Corey T Watson

Immunoglobulins (IGs), critical components of the human immune system, are composed of heavy and light protein chains encoded at three genomic loci. The IG Kappa (IGK) chain locus consists of two large, inverted segmental duplications. The complexity of the IG loci has hindered use of standard high-throughput methods for characterizing genetic variation within these regions. To overcome these limitations, we use long-read sequencing to create haplotype-resolved IGK assemblies in an ancestrally diverse cohort (n = 36), representing the first comprehensive description of IGK haplotype variation. We identify extensive locus polymorphism, including novel single nucleotide variants (SNVs) and novel structural variants harboring functional IGKV genes. Among 47 functional IGKV genes, we identify 145 alleles, 67 of which were not previously curated. We report inter-population differences in allele frequencies …

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Jun 2024 • arXiv preprint arXiv:2406.18956

Topotaxial Mutual-Exchange Growth of Magnetic Zintl EuInAs Nanowires with Axion Insulator Classification

Man Suk Song, Lothar Houben, Yufei Zhao, Hyeonhu Bae, Nadav Rothem, Ambikesh Gupta, Binghai Yan, Beena Kalisky, Magdalena Zaluska-Kotur, Perla Kacman, Hadas Shtrikman, Haim Beidenkopf

Nanomaterials bring to expression unique electronic properties that promote advanced functionality and technologies. Albeit, nanoscale growth presents paramount challenges for synthesis limiting the diversity in structures and compositions. Here, we demonstrate solid-state topotactic exchange that converts Wurtzite InAs nanowires into Zintl phase EuInAs nanowires. In situ evaporation of Eu and As over InAs nanowire cores in molecular beam epitaxy results in mutual exchange of Eu from the shell and In from the core. A continuous EuInAs shell thereby grows that gradually consumes the InAs core and converts it into a single phase EuInAs nanowire. Topotaxy, which facilitates the mutual exchange, is supported by the substructure of the As matrix which is similar across the Wurtzite InAs and Zintl EuInAs. We provide initial evidence of an antiferromagnetic transition at T 6.5 K in the Zintl phase EuInAs nanowires. Ab initio calculation confirms the antiferromagnetic state and classifies EuInAs as a axion insulator hosting both chiral hinge modes and unpinned Dirac surface states. The topotactic mutual-exchange growth of Zintl EuInAs nanowires thus enables the exploration of intricate magneto-topological states of nanomaterials. Moreover, it may open the path for topotactic mutual-exchange synthesis of nanowires made of other exotic compounds.

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Jun 2024 • Nonlinear Optics and its Applications 2024, PC1300408, 2024

Aharonov-Bohm effect in the time domain

Moti Fridman

Temporal optics revolutionize the field of ultrafast detection with time-lens and time-stretch schemes. We developed a temporal interferometer that enables us to measure ultrafast phase shifts. With this interferometer, we measured phase shifts of correlated beams traveling in different temporal trajectories. This allows us to demonstrate the Aharonov-Bohm effect in the time domain. We developed the theoretical basis of this temporal Aharonov-Bohm effect and showed it in experimental measurements. In the talk, we will explain this effect, describe the experimental setup, and show the results.

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Jun 2024 • Metamaterials XIV, PC129901G, 2024

Mapping local optical constants in deep-subwavelength resonant structures of ultra-high index topological insulators Bi2Se3 and Bi2Te3

Sukanta Nandi, Shany Cohen, Danveer Singh, Michal Poplinger, Pilkhaz Nanikashvili, Doron Naveh, Tomer Lewi

Optical properties of chalcogenide topological insulators (TIs), namely, Bi2Se3 (BS) and Bi2Te3 (BT) were studied across the NIR to MIR spectral ranges. In this spectral range, the experimentally measured optical constants revealed an extremely high permittivity values amounting to refractive indices as high as n≈11 and n≈6.4, for BT and BS respectively. These ultra-high index values were then utilized for demonstrating ultracompact, deep-subwavelength nanostructures (NSs), with unit cell sizes down to ~λ/10. Finally, using scattering-type Scanning Near-field Optical Microscopy (s-SNOM), local variations in the optical constants of these nanostructured TIs were studied. Nanoscale phase mapping on a BS NS revealed the role of the imaginary component of the refractive index in the observed phase shifts, varying from as low as ~0.37π to a maximum of ~2π radians across a resonance. This work thus highlights …

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May 2024 • Briefings in Bioinformatics

Guidelines for reproducible analysis of adaptive immune receptor repertoire sequencing data

Ayelet Peres, Vered Klein, Boaz Frankel, William Lees, Pazit Polak, Mark Meehan, Artur Rocha, João Correia Lopes, Gur Yaari

Enhancing the reproducibility and comprehension of adaptive immune receptor repertoire sequencing (AIRR-seq) data analysis is critical for scientific progress. This study presents guidelines for reproducible AIRR-seq data analysis, and a collection of ready-to-use pipelines with comprehensive documentation. To this end, ten common pipelines were implemented using ViaFoundry, a user-friendly interface for pipeline management and automation. This is accompanied by versioned containers, documentation and archiving capabilities. The automation of pre-processing analysis steps and the ability to modify pipeline parameters according to specific research needs are emphasized. AIRR-seq data analysis is highly sensitive to varying parameters and setups; using the guidelines presented here, the ability to reproduce previously published results is demonstrated. This work promotes transparency …

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May 2024 • Energy Storage Materials

Unleashing the impact of Nb-doped, single crystal, cobalt-free P2-type Na0. 67Ni0. 33Mn0. 67O2 on elevating the cycle life of sodium-ion batteries

Abhinanda Sengupta, Ajit Kumar, Amreen Bano, Aakash Ahuja, Harshita Lohani, Sri Harsha Akella, Pratima Kumari, Malachi Noked, Dan T Major, Sagar Mitra

A synergistic stabilization effect in a Nb-doped P2-type single crystal cobalt-free layered oxide cathode material, offering remarkable cycling stability and high-power performance for Na-ion batteries have unveiled in this study. The introduction of Nb in the transition metal layer not only reduces the electronic band gap but also enhances electronic conductivity and mitigates ionic diffusion energy barriers. The induction of a robust Nb-O bond expedites electron and Na+ transfer, contributing to the stabilization of the host structure is further confirmed through the density functional theory calculations, including electron localization function (ELF) and crystal orbital Hamiltonian population (COHP). To the best of our knowledge, this study is the first to demonstrate a homogeneous distribution of niobium throughout the single crystal, specifically doped at the nickel site within the bulk, without inducing atomic-scale surface …

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May 2024 • Langmuir

Long-Chain Lipids Facilitate Insertion of Large Nanoparticles into Membranes of Small Unilamellar Vesicles

Adan Marzouq, Lion Morgenstein, Carlos A Huang-Zhu, Shimon Yudovich, Ayelet Atkins, Asaf Grupi, Reid C Van Lehn, Shimon Weiss

Insertion of hydrophobic nanoparticles into phospholipid bilayers is limited to small particles that can incorporate into a hydrophobic membrane core between two lipid leaflets. Incorporation of nanoparticles above this size limit requires the development of challenging surface engineering methodologies. In principle, increasing the long-chain lipid component in the lipid mixture should facilitate incorporation of larger nanoparticles. Here, we explore the effect of incorporating very long phospholipids (C24:1) into small unilamellar vesicles on the membrane insertion efficiency of hydrophobic nanoparticles that are 5–11 nm in diameter. To this end, we improve an existing vesicle preparation protocol and utilized cryogenic electron microscopy imaging to examine the mode of interaction and evaluate the insertion efficiency of membrane-inserted nanoparticles. We also perform classical coarse-grained molecular …

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May 2024 • ACS nano, 2024

Mechanisms and Barriers in Nanomedicine: Progress in the Field and Future Directions

Thomas Anchordoquy, Natalie Artzi, Irina V Balyasnikova, Yechezkel Barenholz, Ninh M La-Beck, Jacob S Brenner, Warren CW Chan, Paolo Decuzzi, Agata A Exner, Alberto Gabizon, Biana Godin, Samuel K Lai, Twan Lammers, Michael J Mitchell, S Moein Moghimi, Vladimir R Muzykantov, Dan Peer, Juliane Nguyen, Rachela Popovtzer, Madison Ricco, Natalie J Serkova, Ravi Singh, Avi Schroeder, Anna A Schwendeman, Joelle P Straehla, Tambet Teesalu, Scott Tilden, Dmitri Simberg

In recent years, steady progress has been made in synthesizing and characterizing engineered nanoparticles, resulting in several approved drugs and multiple promising candidates in clinical trials. Regulatory agencies such as the Food and Drug Administration and the European Medicines Agency released important guidance documents facilitating nanoparticle-based drug product development, particularly in the context of liposomes and lipid-based carriers. Even with the progress achieved, it is clear that many barriers must still be overcome to accelerate translation into the clinic. At the recent conference workshop “Mechanisms and Barriers in Nanomedicine” in May 2023 in Colorado, U.S.A., leading experts discussed the formulation, physiological, immunological, regulatory, clinical, and educational barriers. This position paper invites open, unrestricted, nonproprietary discussion among senior faculty, young …

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May 2024 • Nature Communications

Extreme magnetoresistance at high-mobility oxide heterointerfaces with dynamic defect tunability

DV Christensen, TS Steegemans, T D. Pomar, YZ Chen, A Smith, VN Strocov, B Kalisky, N Pryds

Magnetic field-induced changes in the electrical resistance of materials reveal insights into the fundamental properties governing their electronic and magnetic behavior. Various classes of magnetoresistance have been realized, including giant, colossal, and extraordinary magnetoresistance, each with distinct physical origins. In recent years, extreme magnetoresistance (XMR) has been observed in topological and non-topological materials displaying a non-saturating magnetoresistance reaching 103−108% in magnetic fields up to 60 T. XMR is often intimately linked to a gapless band structure with steep bands and charge compensation. Here, we show that a linear XMR of 80,000% at 15 T and 2 K emerges at the high-mobility interface between the large band-gap oxides γ-Al2O3 and SrTiO3. Despite the chemically and electronically very dissimilar environment, the temperature/field phase diagrams of γ-Al2O …

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May 2024 • Histochemistry and Cell Biology

CCAT1 lncRNA is chromatin-retained and post-transcriptionally spliced

Chaya Bohrer, Eli Varon, Eldar Peretz, Gita Reinitz, Noa Kinor, David Halle, Aviram Nissan, Yaron Shav-Tal

Super-enhancers are unique gene expression regulators widely involved in cancer development. Spread over large DNA segments, they tend to be found next to oncogenes. The super-enhancer c-MYC locus forms long-range chromatin looping with nearby genes, which brings the enhancer and the genes into proximity, to promote gene activation. The colon cancer-associated transcript 1 (CCAT1) gene, which is part of the MYC locus, transcribes a lncRNA that is overexpressed in colon cancer cells through activation by MYC. Comparing different types of cancer cell lines using RNA fluorescence in situ hybridization (RNA FISH), we detected very prominent CCAT1 expression in HeLa cells, observed as several large CCAT1 nuclear foci. We found that dozens of CCAT1 transcripts accumulate on the gene locus, in addition to active transcription occurring from the gene. The accumulating transcripts are released …

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May 2024 • arXiv preprint arXiv:2405.21041

Interferometry of quantum correlation functions to access quasiprobability distribution of work

Santiago Hernández-Gómez, Takuya Isogawa, Alessio Belenchia, Amikam Levy, Nicole Fabbri, Stefano Gherardini, Paola Cappellaro

The Kirkwood-Dirac quasiprobability distribution emerges from the quantum correlation function of two observables measured at distinct times and is therefore relevant for fundamental physics and quantum technologies. These quasiprobabilities follow all but one of Kolmogorov axioms for joint probability distributions: they can take non-positive values. Their experimental reconstruction becomes challenging when expectation values of incompatible observables are involved. Previous strategies aimed to reconstruct them using weak measurements or combining strong measurements. Here, we use a more direct approach, an interferometric scheme aided by an auxiliary system, to reconstruct the Kirkwood-Dirac quasiprobability distribution. We experimentally demonstrate the interferometric scheme in an electron-nuclear spin system associated with a nitrogen-vacancy center in diamond. By measuring the characteristic function, we reconstruct the quasiprobability distribution of the work and analyze the behavior of the first and second moments of work. Our results clarify the physical meaning of the work quasiprobability distribution in the context of quantum thermodynamics. Finally, having measured the real and imaginary parts of the Kirkwood-Dirac quasiprobability of work, we are also able to study the uncertainty of measuring the Hamiltonian of the system at two times, via the Robertson-Schr{\"o}dinger uncertainty relation, for different initial states.

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May 2024 • Sensors and Actuators B: Chemical

Energy-efficient NO2 sensors based on two-dimensional layered 2H-WS2 nanosheets

Abderrahim Moumen, Rajashree Konar, Dario Zappa, Eti Teblum, Gilbert Daniel Nessim, Elisabetta Comini

Layered transition metal dichalcogenides (TMDCs) are considered among the next-generation materials for gas sensing. Here, we report exfoliated 2 H-WS 2 nanosheets for the fabrication of highly performing NO 2 sensors. Thermal annealing at several temperatures was performed to investigate the oxidation of WS 2. The long-term stability of 2 H-WS 2 bulk was verified. Using droplet variation method, three batches of conductometric sensors from 2 H-WS 2 dispersions were fabricated on electrical transducers, namely two layers (2 L), five layers (5 L) and ten layers (10 L) WS 2 nanosheets. These sensors were tested towards low NO 2 concentrations at different temperatures (Room Temperature (20℃), 50℃ and 100℃) and relative humidity (RH) levels (20%, 40%, 60%, 80% and 90% RH). 2 L-WS 2 based sensor showed the highest response at room temperature (RT). Excellent repeatability (4 cycles) towards 1 …

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May 2024 • Angewandte Chemie International Edition

Differential Substrate Sensing in Terpene Synthases from Plants and Microorganisms: Insight from Structural, Bioinformatic, and EnzyDock Analyses

Renana Schwartz, Shani Zev, Dan T Major

Terpene synthases (TPSs) catalyze the first step in the formation of terpenoids, which comprise the largest class of natural products in nature. TPSs employ a family of universal natural substrates, composed of isoprenoid units bound to a diphosphate moiety. The intricate structures generated by TPSs are the result of substrate binding and folding in the active site, enzyme‐controlled carbocation reaction cascades, and final reaction quenching. A key unaddressed question in class I TPSs is the asymmetric nature of the diphosphate‐(Mg2+)3 cluster, which forms a critical part of the active site. In this asymmetric ion cluster, two diphosphate oxygen atoms protrude into the active site pocket. The substrate hydrocarbon tail, which is eventually molded into terpenes, can bind to either of these oxygen atoms, yet to which is unknown. Herein, we employ structural, bioinformatics, and EnzyDock docking tools to address this …

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May 2024 • Advances in Cement Research

Enhancing cement hydration by core/shell PS@SiO2 nanoparticles

Meytal Shalit, Maya Radune, Yaniv Knop, Yitzhak Mastai

Nanoparticles are widely used in construction. Here, nano-SiO2 is employed, in a way that prevents agglomeration of the nanoparticles, as pozzolanic material to improve Portland cement hydration and to improve the properties of the concrete. To explore the effect of nano-SiO2 and core-shell PS@SiO2 on cement properties, spherical polystyrene particles were prepared by dispersion polymerization of styrene in polar solvents and characterized by FTIR and E-SEM. The core shells PS@SiO2 were synthesized by Stöber method. The results showed an amorphous nano-SiO2 layer can be deposited uniformly on polystyrene particles. This core/shell structure was reducing the aggregation of nano-SiO2 effectively. It was shown that PS@SiO2 particles improved the concrete performances compared to blended cement with nano-SiO2 due to the agglomeration affect. Highlights •Core/shell PS@SiO2 nanoparticles …

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May 2024 • Cell Reports

Structural and mechanistic insights into the function of Leishmania ribosome lacking a single pseudouridine modification

K Shanmugha Rajan, Saurav Aryal, Disha-Gajanan Hiregange, Anat Bashan, Hava Madmoni, Mika Olami, Tirza Doniger, Smadar Cohen-Chalamish, Pascal Pescher, Masato Taoka, Yuko Nobe, Aliza Fedorenko, Tanaya Bose, Ella Zimermann, Eric Prina, Noa Aharon-Hefetz, Yitzhak Pilpel, Toshiaki Isobe, Ron Unger, Gerald F Späth, Ada Yonath, Shulamit Michaeli

Leishmania is the causative agent of cutaneous and visceral diseases affecting millions of individuals worldwide. Pseudouridine (Ψ), the most abundant modification on rRNA, changes during the parasite life cycle. Alterations in the level of a specific Ψ in helix 69 (H69) affected ribosome function. To decipher the molecular mechanism of this phenotype, we determine the structure of ribosomes lacking the single Ψ and its parental strain at ∼2.4–3 Å resolution using cryo-EM. Our findings demonstrate the significance of a single Ψ on H69 to its structure and the importance for its interactions with helix 44 and specific tRNAs. Our study suggests that rRNA modification affects translation of mRNAs carrying codon bias due to selective accommodation of tRNAs by the ribosome. Based on the high-resolution structures, we propose a mechanism explaining how the ribosome selects specific tRNAs.

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May 2024 • Crystal Growth & Design

Enantioselective Crystallization of Naturally Chiral Ag2CO3 Crystals Insights into the Influence of Chiral Additives

Gil Otis, Matan Oliel, Subhomoy Das, Yarden Ben Moshe, Yulia Shenberger, Sharon Ruthstein, Yitzhak Mastai

Chiral induction of chiral crystals attracts significant attention due to its implications for developing chiral materials and understanding mechanisms of symmetry breaking enantioselective crystallization of naturally chiral inorganic crystals and their potential use in chiral discrimination, which are, however, largely unexplored. Here, we investigate the chiral induction during the crystallization of naturally chiral Ag2CO3 crystals using arginine amino acid as the chiral inducer. The chiral nature of Ag2CO3 was evaluated using various techniques. Chiral crystals exhibited chiral selective binding toward different amino acid enantiomers. The significant selectivity in adsorption was confirmed by circular dichroism, high-performance liquid chromatography, and isothermal titration calorimetry. Understanding chiral induction in crystal growth may open avenues for the controlled assembly of chiral materials and the development …

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May 2024 • Energy Storage Materials

Self-discharge in flowless Zn-Br2 batteries and its mitigation

Elad Ballas, Amey Nimkar, Gil Bergman, Ran Elazari, Racheli Wakshlak, Daniel Sharon, Mikhael D Levi, Dan Thomas Major, Daniel Mandler, Netanel Shpigel, Doron Aurbach

Several decades after the invention of the flow Zn-Br2 systems persistent attempts have been made to develop stationary Zn-Br2 batteries. Such development should increase the energy density of the system simultaneously significantly reducing their cost and opening new challenges associated with the cell design and its performance. One of the major concerns is the rapid self-discharge of stationary systems leading to spontaneous charge loss during battery storage time. While self-discharge in flow cells is generally attributed to the chemical oxidation of the Zn anode, we show that the origin of self-discharge in a static configuration is completely different. By systematic investigations of activated carbon with different surface areas under varied charging conditions, mechanistic insights into this phenomenon were provided. Based on this understanding, we proposed herein an effective way to suppress the cathode …

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May 2024 • Biotechnology Journal

DNA origami scaffold promoting nerve guidance and regeneration

Jonathan Giron, Merav Antman‐Passig, Neta Zilony, Hadas Schori, Ido Bachelet, Orit Shefi

Self‐assembly of biological elements into biomimetic cargo carriers for targeting and delivery is a promising approach. However, it still holds practical challenges. We developed a functionalization approach of DNA origami (DO) nanostructures with neuronal growth factor (NGF) for manipulating neuronal systems. NGF bioactivity and its interactions with the neuronal system were demonstrated in vitro and in vivo models. The DO elements fabricated by molecular self‐assembly have manipulated the surrounding environment through static spatially and temporally controlled presentation of ligands to the cell surface receptors. Our data showed effective bioactivity in differentiating PC12 cells in vitro. Furthermore, the DNA origami NGF (DON) affected the growth directionality and spatial capabilities of dorsal root ganglion neurons in culture by introducing a chemotaxis effect along a gradient of functionalized DO …

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