Article
Physics, Fluids & Plasmas
Lili Zeng, Walter W. Reisner
Summary: In this study, molecular dynamics simulation was used to investigate the nonequilibrium physics of single nanochannel-confined semiflexible polymers in a homogeneous flow field. The results showed that the flow-based compression of the polymer against the end of the nanochannel led to a distinct organization of folds and circular coils. The organization varied with the stiffness of the chains and the flow speed, but was ultimately determined by the minimization of the total chain free energy.
Article
Chemistry, Multidisciplinary
Xuanhui Meng, Philipp Kukura, Sanli Faez
Summary: This study presents a molecular force sensor and charge detector based on tracking tethered double-stranded DNA functionalised with charged nanoparticles. The approach allows for real-time detection and quantification of electrophoretic force and changes in particle charge state down to the sub-piconewton scale, providing an alternative route for studying structural and charge dynamics at the single molecule level.
Article
Biochemical Research Methods
Hugh Wilson, Quan Wang
Summary: ABEL-FRET is an immobilization-free platform with ultrahigh resolution in FRET efficiency, providing additional size and shape information through single-molecule diffusivity for a holistic and dynamic view of biomolecules.
Article
Multidisciplinary Sciences
Tejeshwar C. Rao, Alexa L. Mattheyses
Summary: Multicellular organisms rely on interactions between membrane receptors and cognate ligands in the ECM to coordinate various functions. Mechanical forces can be transmitted through cell adhesion receptors to ligands in the ECM. Currently available tools for quantifying cell mechanics and relating them to focal adhesions, cellular morphology, and signaling are limited. Tension gauge tethers (TGTs), a type of DNA-based molecular force sensors, have been used to measure these changes. TGT probes can modulate force thresholds and report receptor forces at diffraction-limited resolution. This article describes a protocol using TGTs to study the impact of EGFR on integrin mechanics and adhesion formation.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Chemistry, Multidisciplinary
Zilong Guo, Haiyan Hong, Hao Sun, Xiaofeng Zhang, Chen-Xu Wu, Bing Li, Yi Cao, Hu Chen
Summary: Single molecule force spectroscopy is a powerful tool for studying protein folding dynamics and other mechanobiological processes, but high force precision does not guarantee high force accuracy. The challenge in magnetic tweezers lies in accurately determining applied forces due to calibration uncertainties.
Article
Physics, Fluids & Plasmas
Narender Khatri, P. S. Burada
Summary: This study introduces a mechanism to separate particles of different masses in a microfluidic channel using oscillatory force and static bias, providing a way to design lab-on-a-chip devices for particle separation.
Article
Chemistry, Physical
Jung-uk Lee, Wookjin Shin, Yongjun Lim, Jungsil Kim, Woon Ryoung Kim, Heehun Kim, Jae-Hyun Lee, Jinwoo Cheon
Summary: m-Torquer is a magnetic toolkit that mimics magnetoreception in nature, providing precise stimulation to cells and reliable neuromodulation in animals like mice. Its versatility allows for a wide range of applications, potentially even in large animals such as primates.
Article
Chemistry, Analytical
Zimeng Wang, Ping Wang, Chunxian Tao, Dawei Zhang, Zhenqing Li, Yoshinori Yamaguchi
Summary: Capillary gel electrophoresis using a controllable pore-size hydrogel can achieve a homogenous structure suitable for DNA separation based on the molecular weights of PA and PS. This hydrogel allows for efficient resolution of DNA fragments smaller than 1500 bp and more than 100 consecutive runs before performance degradation. Notably, the hydrogel can separate dsDNA up to single base pair resolution and differentiate dsDNA of the same length with 1 bp difference.
ANALYTICA CHIMICA ACTA
(2021)
Article
Physics, Fluids & Plasmas
Dibyajyoti Mohanta, Debaprasad Giri, Sanjay Kumar
Summary: This study investigates the migration of a polymer chain across an entropic trap using the lattice model and exact enumeration technique. The effects of solvent gradient in the trap on the migration process are explored.
Article
Infectious Diseases
Hung-Jen Tang, Yi-Tsung Lin, Chi-Chung Chen, Chih-Wei Chen, Ying-Chen Lu, Wen-Chien Ko, Hung-Jui Chen, Bo-An Su, Ping-Chin Chang, Yin-Ching Chuang, Chih-Cheng Lai
Summary: The study revealed that E. anophelis isolates were susceptible to certain antibiotics, with the combination of minocycline and cefoperazone/sulbactam showing the best synergistic effects in combating biofilm formation of clinical isolates. Additionally, novel mutations were identified, indicating antibiotic resistance mechanisms.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Chemistry, Organic
Tamilselvan Rajasekaran, Graeme C. Freestone, Rodrigo Galindo-Murillo, Barbara Lugato, Hans Gaus, Michael T. Migawa, Eric. E. Swayze, Thomas E. Cheatham III, Punit P. Seth, Stephen Hanessian
Summary: This manuscript describes a chemical strategy to preorganize a trinucleotide subunit in a conformation suitable for base pairing, using bis-phosphonate esters bridging hydrocarbon tethers to create macrocyclic analogues. The synthesis and incorporation of eight P-stereoisomers of these analogues into oligonucleotides (ONs) is described, and their effect on hybridization kinetics with RNA is characterized. The size of the macrocyclic tether and configuration at phosphorus significantly influenced the on-rates and off-rates of the modified ONs. The results highlight the potential of backbone-constrained macrocyclic nucleic acid analogues in modulating hybridization kinetics.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Polymer Science
Rongyan Zhang, Yanwei Wang, Guangcan Yang
Summary: The interaction between DNA and proteins is important for both basic research in biology and potential applications in nanotechnology. This study investigated the complexes formed by lambda DNA and lysozyme in a dilute aqueous solution. It was found that lysozyme effectively neutralizes the positive charge of DNA, inducing charge inversion. The compact and positively charged structure of lysozyme contributes to its high efficiency in charge neutralization. Increasing the concentration of lysozyme leads to changes in both DNA mobility and condensing force, as well as the morphology of the DNA-lysozyme complex.
Article
Chemistry, Analytical
Mario A. Cornejo, Thomas H. Linz
Summary: This report presents a simple and rapid method for directly quantifying multiple miRNAs using microfluidic thermal gel electrophoresis (TGE). The method utilizes fluorescent probes and an innovative microfluidic device to achieve accurate miRNA measurement, and it has been validated with cell extracts. This technique has the potential for automation and can be valuable for clinical and pharmaceutical analyses.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Y. M. Nuwan D. Y. Bandara, Nasim Farajpour, Kevin J. Freedman
Summary: This study presents a thorough investigation of protein sensing under low electrolyte conditions. The unfolding of proteins was found to be correlated with their isoelectric point and sensitive to the applied voltage and pH. The different forces acting on the protein movement also play a critical role.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
E. H. Edinsha Gladis, K. Nagashri, M. Anisha, J. Joseph
Summary: A series of metal complexes containing Phenanthroline scaffold were designed and synthesized to obtain effective anti-cholinesterase activities. The synthesized 1,10-Phenanthroline derivative showed good inhibitory effects against acetylcholinesterase and butyrylcholinesterase.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Multidisciplinary Sciences
Jehangir Cama, Kareem Al Nahas, Marcus Fletcher, Katharine Hammond, Maxim G. Ryadnov, Ulrich F. Keyser, Stefano Pagliara
Summary: This study investigates the structure-activity relationships of polypeptide antibiotics using two microfluidic platforms. The researchers find strong correlations between the physicochemical activity of each peptide at the membrane level and its biological activity at the cellular level. They demonstrate the capability of their strategy to detect differential responses for peptides with single amino acid substitutions, which can accelerate the rational design and development of peptide antimicrobials.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Mohammed F. Alawami, Filip Boskovic, Jinbo Zhu, Kaikai Chen, Sarah E. Sandler, Ulrich F. Keyser
Summary: In this study, 102 quartz glass nanopores with a diameter of 11-18 nm were fabricated using laser-assisted capillary pulling. The use cycles of the nanopores were improved by vacuum storage and minimal washing steps. The single-molecule biosensing capability of the nanopores over repeated use cycles was demonstrated through quantitative analysis of a DNA carrier.
Article
Chemistry, Analytical
Kareem Al Nahas, Marcus Fletcher, Katharine Hammond, Christian Nehls, Jehangir Cama, Maxim G. Ryadnov, Ulrich F. Keyser
Summary: This study used a highly parallelized microfluidic platform to conduct quantitative long-term microscopy studies on the membrane-disruptive activity of antimicrobial peptides, revealing the relationship between the modes of action and the molecular activity mechanisms of these peptides.
ANALYTICAL CHEMISTRY
(2022)
Article
Physics, Condensed Matter
Stuart F. Knowles, Marcus Fletcher, Jeffrey Mc Hugh, Max Earle, Ulrich F. Keyser, Alice L. Thorneywork
Summary: In this study, video microscopy was used to investigate the capture process of colloidal particles transported through microfluidic channels. By analyzing trajectories of particles and changing the height profiles of microfluidic devices, it was found that particle-particle interactions had little effect on the flow field. Furthermore, changing the reservoir geometry led to a transition between long-range attraction of particles and diffusion-to-capture behavior, resulting in qualitative changes in the concentration fields.
JOURNAL OF PHYSICS-CONDENSED MATTER
(2022)
Review
Chemistry, Physical
Mohammad Saghafi, Selvaraj Chinnathambi, Serge G. Lemay
Summary: Electrochemical impedance spectroscopy (EIS) is a powerful tool for probing processes at electrodes. Nanoscale impedance measurements face challenges due to stray capacitance signals from interconnects and faster dynamics of miniaturized electrodes. Recent advances in theoretical understanding and experimental efforts are discussed, with particular emphasis on conceptual and technical aspects.
CURRENT OPINION IN COLLOID & INTERFACE SCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Kaikai Chen, Adnan Choudhary, Sarah E. Sandler, Christopher Maffeo, Caterina Ducati, Aleksei Aksimentiev, Ulrich F. Keyser
Summary: High-resolution analysis of biomolecules has greatly advanced biosensing, but there are limited methods available for high-resolution analysis of unlabeled single molecules in their native states. In this work, label-free electrical sensing of single molecules with nanometer resolution is demonstrated using a narrow solid-state nanopore. The super-resolution ability is attributed to the enhancement of the electric field at the tip of the nanopore induced by nanostructures. This work presents a general approach to improve the resolution of single-molecule nanopore sensing and has implications for label-free high-resolution DNA sequence mapping and digital information storage.
ADVANCED MATERIALS
(2023)
Article
Chemistry, Analytical
Sahana Sarkar, Ab F. Nieuwenhuis, Serge G. Lemay
Summary: We introduced a framework for the fabrication of chip based electrochemical nanogap sensors integrated with micro fluidics. Instead of PDMS, SU-8 aided adhesive bonding of silicon and glass wafers is used to implement parallel flow control. The fabrication process allows large-scale production with high throughput and reproducibility. Moreover, the monolithic structures enable simple electrical and fluidic connections, eliminating the need for specialized equipment. We demonstrated the utility of these flow-incorporated nanogap sensors by conducting redox cycling measurements under laminar flow conditions.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Jinbo Zhu, Ran Tivony, Filip Boskovic, Joana Pereira-Dias, Sarah E. Sandler, Stephen Baker, Ulrich F. Keyser
Summary: In this study, a nanopore sensor based on DNA dumbbell nanoswitches was established for multiplexed nucleic acid detection and bacterial identification. By assembling four DNA dumbbell nanoswitches on one carrier, simultaneous detection of four different sequences of nucleic acids was achieved. The high specificity of the dumbbell nanoswitch was verified by distinguishing single base variants in DNA and RNA targets using barcoded DNA carriers in multiplexed measurements. By combining multiple dumbbell nanoswitches with barcoded DNA carriers, different bacterial species could be identified even with high sequence similarity by detecting strain specific 16S ribosomal RNA (rRNA) fragments.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Raphael P. B. Jacquat, Georg Krainer, Quentin A. E. Peter, Ali Nawaz Babar, Oliver Vanderpoorten, Catherine K. Xu, Timothy J. Welsh, Clemens F. Kaminski, Ulrich F. Keyser, Jeremy J. Baumberg, Tuomas P. J. Knowles
Summary: This paper presents an approach called nanocavity diffusional sizing (NDS) that relies on nanocavity confinement to measure the size of nanoscale particles and single biomolecules in solution. It uses particle residence times within nanofluidic cavities to determine their hydrodynamic radii. Experimental results show that the residence times scale linearly with the sizes of nanoscale colloids, protein aggregates, and single DNA oligonucleotides. NDS offers a new optofluidic approach for rapid and quantitative sizing of nanoscale particles with potential applications in nanobiotechnology, biophysics, and clinical diagnostics.
Article
Nanoscience & Nanotechnology
S. M. Leitao, V. Navikas, H. Miljkovic, B. Drake, S. Marion, G. Pistoletti Blanchet, K. Chen, S. F. Mayer, U. F. Keyser, A. Kuhn, G. E. Fantner, A. Radenovic
Summary: In current nanopore-based label-free single-molecule sensing technologies, stochastic processes make it challenging to control the selection, rate, and velocity of single-molecule translocations. This study proposes a method that uses a glass nanopore mounted on a three-dimensional nanopositioner to spatially select and deterministically translocate molecules tethered on a glass surface. By controlling the distance between the nanopore and glass surface, the region of interest on the molecule can be actively selected and scanned at a controlled number of times and velocity. The method demonstrates versatility in assessing DNA-protein complexes, DNA rulers, and DNA gaps, enabling single-nucleotide gap detection.
NATURE NANOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sophie L. Williams, Corella S. Casas-Delucchi, Federica Raguseo, Dilek Guneri, Yunxuan Li, Masashi Minamino, Emma E. Fletcher, Joseph T. P. Yeeles, Ulrich F. Keyser, Zoe A. E. Waller, Marco Di Antonio, Gideon Coster
Summary: This study investigates the effects of physiological quadruplex secondary structures on genome stability by reconstituting eukaryotic DNA replication in vitro. G-quadruplexes (G4s) and intercalated Motifs (iMs) are found to form during replication and thereby induce replisome stalling, leading to helicase-polymerase uncoupling and nascent DNA breakage. A single physiological G4 or iM structure stalls the eukaryotic replisome by inhibiting leading strand synthesis. Helicase-polymerase uncoupling occurs following replication stalling at G4s. iMs can induce breakage on nascent DNA. Stalled forks at G4s or iMs can be rescued by the accessory helicase Pif1. In vitro reconstitution shows that a single physiological G4 or iM secondary structure stalls the eukaryotic replisome by inhibiting leading strand synthesis.
Article
Chemistry, Multidisciplinary
Yunxuan Li, Sarah E. Sandler, Ulrich F. Keyser, Jinbo Zhu
Summary: Nanopores are powerful single-molecule sensors for identifying and characterizing small polymers like DNA. In this study, a programmable DNA carrier platform was introduced to capture specific DNA nanostructures, and controlled translocation experiments through glass nanopores were conducted to understand the relationship between nanopore signals and DNA physical properties. The results show that the volume and flexibility of DNA nanostructures in the nanopore primarily determine the ionic current drop. Additionally, this understanding of DNA topology allowed discrimination between circular single-stranded DNA molecules and linear ones with the same number of nucleotides using the nanopore signal.
Article
Chemistry, Multidisciplinary
Sara Rocchetti, Alexander Ohmann, Rohit Chikkaraddy, Gyeongwon Kang, Ulrich F. Keyser, Jeremy J. Baumberg
Summary: Developing highly enhanced plasmonic nanocavities allows direct observation of light-matter interactions at the nanoscale. With DNA origami, precise nanopositioning of single-quantum emitters in ultranarrow plasmonic gaps enables detailed study of their modified light emission. By developing nanoparticle-on-mirror constructs with DNA nanostructures as reliable and customizable spacers for nanoparticle binding, it is revealed that the traditional understanding of Purcell-enhanced molecular dye emission is misleading, and the enhanced dipolar dye polarizability greatly amplifies optical forces acting on the facet Au atoms, causing their rapid destabilization. Different dyes exhibit emission spectra dominated by inelastic (Raman) scattering rather than fluorescence, challenging the conventional theories in the field of quantum optics using plasmonics.
Article
Chemistry, Multidisciplinary
Jeffrey Mc Hugh, Stanislaw Makarchuk, Daria Mozheiko, Ana Fernandez-Villegas, Gabriele S. Kaminski Schierle, Clemens F. Kaminski, Ulrich F. Keyser, David Holcman, Nathalie Rouach
Summary: Dendrites and dendritic spines play crucial roles in neuronal communication by conveying information through voltage signals. Using nanopipettes, researchers were able to access and record voltage dynamics in fine dendrites, revealing diverse patterns such as spontaneous transients, bursting events, and oscillations. These voltage patterns were found to be more dependent on synaptic activity than on action potentials, and long-time recordings showed complex dynamics that may contribute to dendritic computations.
Article
Multidisciplinary Sciences
Eva Kreysing, Jeffrey Mc Hugh, Sarah K. Foster, Kurt Andresen, Ryan D. Greenhalgh, Eva K. Pillai, Andrea Dimitracopoulos, Ulrich F. Keyser, Kristian Franze
Review
Chemistry, Multidisciplinary
Yikuan Liu, Xiaona Liu, An Su, Chengtao Gong, Shenwei Chen, Liwei Xia, Chengwei Zhang, Xiaohuan Tao, Yue Li, Yonghe Li, Tulai Sun, Mengru Bu, Wei Shao, Jia Zhao, Xiaonian Li, Yongwu Peng, Peng Guo, Yu Han, Yihan Zhu
Summary: Covalent organic frameworks are crystalline porous materials with designable structures and functions, which can acquire multifunctionalities and have versatile applications in gas separation/storage, catalysis, and optoelectronic devices.
CHEMICAL SOCIETY REVIEWS
(2024)
Review
Chemistry, Multidisciplinary
Heyang Zhang, Jo Vandesompele, Kevin Braeckmans, Stefaan C. De Smedt, Katrien Remaut
Summary: Gene therapy has the potential to revolutionize the treatment of inherited and acquired diseases, but its success rate is currently limited. This review focuses on the obstacles faced by gene therapies in the human body, such as nucleic acid degradation by abundant nucleases, and discusses strategies to reduce degradation and methods to assess nucleic acid integrity.
CHEMICAL SOCIETY REVIEWS
(2024)
Review
Chemistry, Multidisciplinary
Chenxi Duan, Chunming Cui
Summary: Low valent group 14 compounds with diazaborolyl substituents exhibit unique structures and reactivity due to the combination of sigma-electron donation and steric hindrance. The modulation of the HOMO-LUMO gap by the diazaborolyl substituents results in novel reaction patterns in the activation of small molecules and inert chemical bonds.
CHEMICAL SOCIETY REVIEWS
(2024)
Review
Chemistry, Multidisciplinary
David E. Salazar Marcano, Nada D. Savic, Kilian Declerck, Shorok A. M. Abdelhameed, Tatjana N. Parac-Vogt
Summary: Metal-oxo clusters have great potential in various fields and can react with biomolecules, making them promising for applications in disease treatment and energy development. They can also be used in the development of inorganic drugs and bioanalytical tools.
CHEMICAL SOCIETY REVIEWS
(2024)
Review
Chemistry, Multidisciplinary
Lana K. Moree, Logan A. V. Faulkner, James D. Crowley
Summary: In this tutorial review, the general methods for synthesizing heterometallic metallosupramolecular architectures (MSAs), specifically heterometallic cages, are examined. The intrinsic properties and potential applications of these cages as host-guest systems and reaction catalysts are discussed.
CHEMICAL SOCIETY REVIEWS
(2024)