Article
Chemistry, Physical
Meng Yu, Wei Si, Tao Zeng, Chang Chen, Xiaojing Lin, Zhouxiang Ji, Fei Guo, Yuxiang Li, Jingjie Sha, Yuliang Dong
Summary: This research used all-atom molecular dynamic simulations to uncover the microscopic mechanism behind current variation when single-stranded DNA passes through the MspA nanopore. It was found that nucleotide orientation and the region below the constriction of the nanopore play crucial roles in inducing current variation. These findings provide valuable insights for developing low-cost, high-throughput nanopore DNA sequencing technology.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Review
Chemistry, Multidisciplinary
Weichen Wei, Xiaojuan Chen, Xuejiao Wang
Summary: Nanopore sensing technique, as an emerging method for detecting single molecules, has been extensively researched in various fields, including nanopore sequencing and other applications of single-molecule studies. Recently, researchers have explored specific ion effects in nanopore channels, which provide a unique understanding of the Hofmeister effect at the single-molecule level. This review summarizes the recent advances in using nanopore sensing techniques to study the Hofmeister effect and attempts to elucidate the physicochemical mechanism involved. The challenges and future goals in this field are also discussed.
Article
Chemistry, Physical
Xiaodong He, Jialiang Chen
Summary: This study used molecular dynamics simulations to investigate the properties of ionic motion in negatively charged conical nanopores with a fixed tip radius. The effects of electric fields, angles, and cation species on ionic current rectification (ICR) were studied. The results showed that the ion current was mainly contributed by the flow of cations in ultra-narrow nanopores, and the rectification ratio increased linearly with the angle, slowed down and stabilized with the electric fields, and depended on the cation species. The study provides valuable insights into the behavior of ions in ultra-narrow conical nanopores and the mechanisms behind ICR.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Article
Multidisciplinary Sciences
Lauren S. Lastra, Y. M. Nuwan D. Y. Bandara, Michelle Nguyen, Nasim Farajpour, Kevin J. Freedman
Summary: This article investigates the translocation mechanism, pulse direction, and shape in nanopore sensing, and proposes the role of electroosmosis in driving DNA events and conductive events.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Iuliana Soldanescu, Andrei Lobiuc, Mihai Covasa, Mihai Dimian
Summary: Modern biomedical sensing techniques have become more precise and accurate with new technologies that offer speed and specificity for disease markers. Early-stage diagnosis is crucial for successful treatment, but classical methods struggle to detect low concentrations of biomarkers. Biosensors, especially single-molecule sensors like nanopores, are gaining interest in medicine due to their easy operation, speed, and portability, as well as low costs and reliable results. However, the use of nanopores as diagnostic techniques is still in development, with ongoing efforts to stabilize the nanopore structures, enhance chemistries, and improve data collection and bioinformatic analysis.
Article
Biochemistry & Molecular Biology
Punam Rattu, Flo Glencross, Sophie L. Mader, Chris-Kriton Skylaris, Stephen J. Matthews, Sarah L. Rouse, Syma Khalid
Summary: Two proteins, CsgG and CsgF, from the Escherichia coli membrane protein complex are studied as proteinaceous nanopores for DNA sequencing. Molecular dynamics simulations were conducted to characterize their mechanical strength, conformational dynamics, and impact on DNA translocation. The study found that CsgG's barrel is more susceptible to damage from external electric fields compared to the protein vestibule, and the presence of CsgF within the CsgG-CsgF complex enables it to withstand higher electric fields.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Chemistry, Analytical
Essraa A. Hussein, Ryan J. White
Summary: Resistive pulse sensing using ion channel proteins has evolved as a single-molecule approach with high molecular selectivity, but requires a stable lipid membrane. The newly developed gold electrode-supported bilayer technology offers high spatial resolution but suffers from channel current decay. Introducing a silver nanoneedle to support lipid bilayer formation and ion channel measurements can mitigate current decay and produce stable DC channel currents.
ANALYTICAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Jiajun Wang, Jigneshkumar Dahyabhai Prajapati, Fan Gao, Yi-Lun Ying, Ulrich Kleinekathoefer, Mathias Winterhalter, Yi-Tao Long
Summary: Chirality is important but often overlooked in biological and chemical processes due to technical limitations. Researchers have used an electrostatically asymmetric membrane channel to successfully identify chiral amino acids in single peptides. This study provides a new approach for developing chiral recognition and protein sequencing methods.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Physical
Makusu Tsutsui, Kazumichi Yokota, Yuhui He, Tomoji Kawai
Summary: A permittivity gradient approach is reported to amplify the ionic blockade characteristics of DNA in solid-state nanopore sensing. Positive gradients enhance ionic signals, while negative gradients cause adverse effects. This phenomenon provides a novel way to enhance the single-molecule sensitivity of nanopore sensing.
Article
Chemistry, Analytical
Qi Shen, Pan-Ling Zhou, Bin-Tong Huang, Juan Zhou, Hai-Ling Liu, Saud Asif Ahmed, Xin-Lei Ding, Jian Li, Yue-Ming Zhai, Kang Wang
Summary: Gold nanopore is promising for single molecule sequencing, and there is an urgent need for small and size-controllable nanopores. By attaching gold nanoplates to glass nanopipettes using sulfhydryl silane, single molecule detection has been successfully achieved.
JOURNAL OF ELECTROANALYTICAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Juan Zhou, Qing Lan, Wang Li, Li-Na Ji, Kang Wang, Xing-Hua Xia
Summary: Obtaining sequential and conformational information on proteins is important for understanding their functions. This study combines surface enhanced Raman scattering (SERS) with a nanopore to observe the unfolding and multistep sequential translocation of single molecule (SM) cytochrome c (cyt c). The high bias voltage unfolds the SM protein, slowing down the translocation and allowing specific SERS traces of different SM cyt c segments to be recorded. This research provides insight into protein segments and accelerates the development of nanopore-based SM protein sequencing.
Article
Chemistry, Analytical
Xiaohan Chen, Youwen Zhang, Pearl Arora, Xiyun Guan
Summary: Different species can be detected using nanopores engineered with various recognition sites based on non-covalent interactions. This strategy allows for differentiation between species, making it potentially useful for molecular detection in medical and environmental applications.
ANALYTICAL CHEMISTRY
(2021)
Article
Chemistry, Physical
Darya Gurina, Ekaterina Odintsova, Andrei Kolesnikov, Mikhail Kiselev, Yury Budkov
Summary: In this study, the behavior of an ionic liquid in carbon nanopores of different widths was investigated using molecular dynamics simulations. The results showed that the confined ionic liquid exhibited a layering structure and displayed charge overcompensation and lattice saturation effects.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Article
Biochemistry & Molecular Biology
Joseph W. F. Robertson, Madhav L. Ghimire, Joseph E. Reiner
Summary: Protein nanopores have evolved into an important class of sensors for studying biophysical processes and detecting biopolymers. This review focuses on the chemistry of biological pores and its impact on molecular detection at the single molecule scale.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
Article
Chemistry, Multidisciplinary
Wei Si, Xiaojing Lin, Liwei Wang, Gensheng Wu, Yin Zhang, Yunfei Chen, Jingjie Sha
Summary: This study theoretically reports a DNA-tracked nanovehicle that can move on a solid-state surface using molecular dynamics simulations. The nanovehicle is assembled with a graphene membrane as the chassis and circular ssDNAs as the wheels. By inducing electroosmotic flows through independently charged nanopores, controlled rotary motion is achieved, allowing the nanovehicle to move linearly and make turns. This design enables access to almost anywhere in the human body, leading to breakthroughs in nanoscale surgery and drug delivery. It enriches the nanorobot family and provides a new approach for nanovehicle design.
Article
Chemistry, Multidisciplinary
Tobias Ensslen, Kumar Sarthak, Aleksei Aksimentiev, Jan C. Behrends
Summary: The use of a protein nanopore is demonstrated to differentiate posttranslational modifications (PTMs) in proteins or peptides based on the positions of acetylated and methylated lysine residues. This method detects PTMs and their positions by sensing the shape of a fully entrapped peptide, eliminating the need for controlled translocation. This molecular shape-sensing principle offers a versatile, label-free, and high-throughput characterization of protein isoforms.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
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
Biotechnology & Applied Microbiology
Luning Yu, Xinqi Kang, Fanjun Li, Behzad Mehrafrooz, Amr Makhamreh, Ali Fallahi, Joshua C. Foster, Aleksei Aksimentiev, Min Chen, Meni Wanunu
Summary: The electrical current blockade caused by a peptide or protein passing through a nanopore can be used as a fingerprint for molecule identification in biosensor applications. This study presents an enzyme-free method for slow, unidirectional transport of full-length proteins through nanopores. By using a chemically resistant biological nanopore, alpha-hemolysin, and a high concentration guanidinium chloride buffer, protein transport can be propelled by electroosmotic effect. The translocation dynamics of proteins resemble that of single-stranded DNA, and single-translocation events contain enough information for orientation and identity determination with over 90% accuracy using a supervised machine-learning classifier.
NATURE BIOTECHNOLOGY
(2023)
Article
Nanoscience & Nanotechnology
Christopher Maffeo, Lauren Quednau, James Wilson, Aleksei Aksimentiev
Summary: Flowing fluid past chiral objects has been used to power rotary motion in man-made machines for centuries. In nanoscale biological or chemical systems, rotary motion is generated by biasing Brownian motion through cyclic chemical reactions. In this study, we demonstrate that a chiral biological molecule (DNA or RNA duplex) rotates unidirectionally at billions of revolutions per minute when an electric field is applied along the duplex, with the rotation direction determined by the duplex's chirality. The rotation is powered by the drag force of the electro-osmotic flow, mimicking the operating principle of a macroscopic turbine at the nanoscale.
NATURE NANOTECHNOLOGY
(2023)
Article
Chemistry, Physical
Kumar Sarthak, David Winogradoff, Yingda Ge, Sua Myong, Aleksei Aksimentiev
Summary: Proteins with disordered regions are important for cellular signaling and biological condensates, but mutations can lead to neurodegenerative diseases. Molecular dynamics simulations were used to study the effects of different force fields on the structure and dynamics of a protein called FUS. The simulations showed that certain force fields produced conformations within the experimental range and also influenced the stability of RNA-protein complexes. The findings suggest that a combination of protein and RNA force fields can provide an optimal description of proteins with both structured and disordered regions and their interactions with RNA.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Physical
Siddharth Krishnan, Aleksei Aksimentiev, Stuart Lindsay, Dmitry Matyushov
Summary: Single-molecule measurements reveal that proteins without redox cofactors can still exhibit electrical conductance over nanometer scale distances. This is surprising considering the expected time scale for electron transport based on hopping rates and energy barriers. However, molecular dynamics simulations combined with an electron transfer theory show that the unique molecular configurations of non-redox-active proteins allow for long-range conductivity with low reorganization energies. These findings are supported by experimental current decay calculations.
ACS PHYSICAL CHEMISTRY AU
(2023)
Review
Chemistry, Multidisciplinary
Xiaojun Wei, Tadas Penkauskas, Joseph E. Reiner, Celeste Kennard, Mark J. Uline, Qian Wang, Sheng Li, Aleksei Aksimentiev, Joseph W. F. Robertson, Chang Liu
Summary: Biotechnological innovations have advanced large-scale protein studies, but current methods for identifying and quantifying individual proteins are insufficient for single-molecule protein sequencing. Nanopore-inspired systems have been developed for genome sequencing, and are now emerging as tools for protein identification and analysis, with potential for novel protein sequencing. This review summarizes recent advances in biological nanopore sensors for protein sequencing, including amino acid identification, controlled translocation of peptides and proteins, and device and algorithm development supported by simulations. The review highlights the need for collaborative efforts across multiple disciplines to enable practical implementation of nanopore-based protein sequencing.
Correction
Biotechnology & Applied Microbiology
Luning Yu, Xinqi Kang, Fanjun Li, Behzad Mehrafrooz, Amr Makhamreh, Ali Fallahi, Joshua C. Foster, Aleksei Aksimentiev, Min Chen, Meni Wanunu
NATURE BIOTECHNOLOGY
(2023)
Article
Nanoscience & Nanotechnology
Xin Shi, Anna-Katharina Pumm, Christopher Maffeo, Fabian Kohler, Elija Feigl, Wenxuan Zhao, Daniel Verschueren, Ramin Golestanian, Aleksei Aksimentiev, Hendrik Dietz, Cees Dekker
Summary: In this study, we experimentally demonstrate the feasibility of developing functional synthetic turbines at the nanoscale by rationally designing nanoscale DNA origami turbines. These turbines can utilize transmembrane electrochemical potentials to rotate autonomously and operate in physiological conditions. This research opens new possibilities for engineering active robotics at the nanoscale.
NATURE NANOTECHNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Wei Si, Xiaojing Lin, Liwei Wang, Gensheng Wu, Yin Zhang, Yunfei Chen, Jingjie Sha
Summary: This study theoretically reports a DNA-tracked nanovehicle that can move on a solid-state surface using molecular dynamics simulations. The nanovehicle is assembled with a graphene membrane as the chassis and circular ssDNAs as the wheels. By inducing electroosmotic flows through independently charged nanopores, controlled rotary motion is achieved, allowing the nanovehicle to move linearly and make turns. This design enables access to almost anywhere in the human body, leading to breakthroughs in nanoscale surgery and drug delivery. It enriches the nanorobot family and provides a new approach for nanovehicle design.
Article
Chemistry, Multidisciplinary
Yin Zhang, Xiang Lian, Wei Si, Jingjie Sha, Yunfei Chen
Summary: Understanding the origin of ionic conductance modulation in nanopore sensors is crucial for precise measurement of analytes on a single molecule level. Previous models focused on high ionic strength based on geometry and independent of applied voltage. However, our numerical simulations reveal that both electroosmotic flow and ionic concentration polarization are influenced by applied voltage, affecting ionic conductance. DNA translocation enhances the effects, resulting in voltage-dependent conductance blockades. These findings provide valuable insights for nanopore sensor design.
MATERIALS CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Multidisciplinary
Chaofan Ma, Wei Xu, Wei Liu, Changhui Xu, Wei Si, Jingjie Sha
Summary: Inspired by nature, nanomotors have been developed that have great potential in microfluidics and biomedical applications. The rotary nanomotor, made up of carbon nanotubes (CNTs) and a circular single-stranded DNA (ssDNA), can be controlled by selectively manipulating ion transport through charged nanopores. The rotation of the nanomotor is driven by the electroosmotic flow (EOF) generated by the oppositely charged dual nanopores, resulting in promising opportunities for precise control of nanomotors.
Article
Chemistry, Physical
Wei Si, Liwei Wang, Xiaojing Lin, Gensheng Wu, Yin Zhang, Jingjie Sha
Summary: Micro/nano manipulation technologies show great potential in accurate surgery and precision medicine development. Scientists have designed and manipulated nanoscale devices and tools for surgical functions targeting cells and tissues. A theoretical nanoscale telescopic arm manipulated by charge-tunable multi-walled carbon nanotubes is proposed in this work to enhance the functionality of nanomachines. Controlled manipulations of the telescopic arm are achieved through predesigned encoding strategies and molecular dynamics simulations, mimicking nanoscale surgeries.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Chemistry, Physical
Prabhat Tripathi, Behzad Mehrafrooz, Aleksei Aksimentiev, Sophie E. Jackson, Martin Gruebele, Meni Wanunu
Summary: This study investigates the behavior of knotted protein structures during translocation through a pore. Using single molecule nanopore experiments and all-atom MD simulations, the researchers observed an unusual behavior in which the rate of translocation plateaus or slows down as the electric potential driving the reaction increases. This study sheds light on the influence of topology on the forced translocation of knotted proteins.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Merle Scherf, Florian Scheffler, Christopher Maffeo, Ulrich Kemper, Jingjing Ye, Aleksei Aksimentiev, Ralf Seidel, Uta Reibetanz
Summary: The development of DNA origami technique has inspired the use of three-dimensional DNA cages for targeted drug delivery. This study presents a method using DNA origami nanotubes for efficient loading and retention of cargo molecules within the DNA cages.