@article {389, title = {A DNA turbine powered by a transmembrane potential across a nanopore}, journal = {Nature Nanotechnology}, volume = {19}, year = {2024}, month = {03/2024}, pages = {338--344}, chapter = {338}, abstract = {

Rotary motors play key roles in energy transduction, from macroscale windmills to nanoscale turbines such as ATP synthase in cells. Despite our abilities to construct engines at many scales, developing functional synthetic turbines at the nanoscale has remained challenging. Here, we experimentally demonstrate rationally designed nanoscale DNA origami turbines with three chiral blades. These DNA nanoturbines are 24{\textendash}27 nm in height and diameter and can utilize transmembrane electrochemical potentials across nanopores to drive DNA bundles into sustained unidirectional rotations of up to 10 revolutions s-1. The rotation direction is set by the designed chirality of the turbine. All-atom molecular dynamics simulations show how hydrodynamic flows drive this turbine. At high salt concentrations, the rotation direction of turbines with the same chirality is reversed, which is explained by a change in the anisotropy of the electrophoretic mobility. Our artificial turbines operate autonomously in physiological conditions, converting energy from naturally abundant electrochemical potentials into mechanical work. The results open new possibilities for engineering active robotics at the nanoscale.

}, issn = {1748-3395}, doi = {10.1038/s41565-023-01527-8}, url = {https://doi.org/10.1038/s41565-023-01527-8}, author = {Shi, Xin and Pumm, Anna-Katharina and Maffeo, Christopher and Kohler, Fabian and Feigl, Elija and Zhao, Wenxuan and Verschueren, Daniel and Golestanian, Ramin and Aksimentiev, Aleksei and Dietz, Hendrik and Dekker, Cees} } @article {399, title = {Conformation-Dependent Hydrogen-Bonding Interactions in a Switchable Artificial Metalloprotein}, journal = {Biochemistry}, year = {2024}, abstract = {

Hydrogen-bonding (H-bonding) interactions in metalloprotein active sites can critically regulate enzyme function. Changes in the protein structure triggered by interplay with substrates, products, and partner proteins are often translated to the metallocofactor by way of specific changes in H-bond networks connected to the active site. However, the complexities of metalloprotein architecture and mechanism often preclude our ability to define the precise molecular interactions giving rise to these intricate regulatory pathways. To address this shortcoming, we have developed conformationally switchable artificial metalloproteins (swArMs) in which allosteric Gln-binding triggers protein conformational changes that impact the microenvironment surrounding an installed metallocofactor. Herein, we report a combined structural, spectroscopic, and computational approach to enhance the conformation-dependent changes in H-bond interactions surrounding the metallocofactor site of a swArM. Structure-informed molecular dynamics simulations were employed to predict point mutations that could enhance active site H-bond interactions preferentially in the Gln-bound\ holo-conformation of the swArM. Testing our predictions via the unique infrared spectral signals associated with the metallocofactor site, we have identified three key residues capable of imparting conformational control over the metallocofactor microenvironment. The resultant swArMs not only model biologically relevant structural regulation but also provide an enhanced Gln-responsive biological probe to be leveraged in future biosensing applications.

}, doi = {10.1021/acs.biochem.4c00209}, url = {https://doi.org/10.1021/acs.biochem.4c00209}, author = {Fatima, Saman and Mehrafrooz, Behzad and Boggs, David G. and Ali, Noor and Singh, Swapnil and Thielges, Megan C. and Bridwell-Rabb, Jennifer and Aksimentiev, Aleksei and Olshansky, Lisa} } @article {397, title = {Dehydrated Biomimetic Membranes with Skinlike Structure and Function}, journal = {ACS Applied Materials \& Interfaces}, volume = {16}, year = {2024}, pages = {20865-20877}, abstract = {

Novel vapor-permeable materials are sought after for applications in protective wear, energy generation, and water treatment. Current impermeable protective materials effectively block harmful agents but trap heat due to poor water vapor transfer. Here we present a new class of materials, vapor permeable dehydrated nanoporous biomimetic membranes (DBMs), based on channel proteins. This application for biomimetic membranes is unexpected as channel proteins and biomimetic membranes were assumed to be unstable under dry conditions. DBMs mimic human skin{\textquoteright}s structure to offer both high vapor transport and small molecule exclusion under dry conditions. DBMs feature highly organized pores resembling sweat pores in human skin, but at super high densities (\>1012\ pores/cm2). These DBMs achieved exceptional water vapor transport rates, surpassing commercial breathable fabrics by up to 6.2 times, despite containing \>2 orders of magnitude smaller pores (1 nm vs \>700 nm). These DBMs effectively excluded model biological agents and harmful chemicals both in liquid and vapor phases, again in contrast with the commercial breathable fabrics. Remarkably, while hydrated biomimetic membranes were highly permeable to liquid water, they exhibited higher water resistances after dehydration at values \>38 times that of commercial breathable fabrics. Molecular dynamics simulations support our hypothesis that dehydration induced protein hydrophobicity increases which enhanced DBM performance. DBMs hold promise for various applications, including membrane distillation, dehumidification, and protective barriers for atmospheric water harvesting materials.

}, doi = {10.1021/acsami.3c19572}, url = {https://doi.org/10.1021/acsami.3c19572}, author = {Oh, Hyeonji and Tu, Yu-Ming and Samineni, Laximicharan and De Respino, Sophie and Mehrafrooz, Behzad and Joshi, Himanshu and Massenburg, Lynnicia and Lopez-Marques, Horacio and Elessawy, Nada and Song, Woochul and Behera, Harekrushna and Dhiman, Raman and Boorla, Veda Sheersh and Kher, Kartik and Lin, Yi-Chih and Maranas, Costas and Aksimentiev, Aleksei and D. Freeman, Benny and Kumar, Manish} } @article {384, title = {Unidirectional single-file transport of full-length proteins through a nanopore}, journal = {Nature Biotechnology}, volume = {41}, year = {2023}, month = {01/2023}, pages = {1130--1139}, abstract = {

The electrical current blockade of a peptide or protein threading through a nanopore can be used as a fingerprint of the molecule in biosensor applications. However, threading of full-length proteins has only been achieved using enzymatic unfolding and translocation. Here we describe an enzyme-free approach for unidirectional, slow transport of full-length proteins through nanopores. We show that the combination of a chemically resistant biological nanopore, α-hemolysin (narrowest part is \textasciitilde1.4\thinspacenm in diameter), and a high concentration guanidinium chloride buffer enables unidirectional, single-file protein transport propelled by an electroosmotic effect. We show that the mean protein translocation velocity depends linearly on the applied voltage and translocation times depend linearly on length, resembling the translocation dynamics of ssDNA. Using a supervised machine-learning classifier, we demonstrate that single-translocation events contain sufficient information to distinguish their threading orientation and identity with accuracies larger than 90\%. Capture rates of protein are increased substantially when either a genetically encoded charged peptide tail or a DNA tag is added to a protein.

}, issn = {1546-1696}, doi = {10.1038/s41587-022-01598-3}, url = {https://doi.org/10.1038/s41587-022-01598-3}, author = {Yu, Luning and Kang, Xinqi and Li, Fanjun and Mehrafrooz, Behzad and Makhamreh, Amr and Fallahi, Ali and Foster, Joshua C. and Aksimentiev, Aleksei and Chen, Min and Wanunu, Meni} } @article {374, title = {Discrimination of RNA fiber structures using solid-state nanopores}, journal = {Nanoscale}, volume = {14}, year = {2022}, month = {05/2023}, pages = {6866-6875}, abstract = {

RNA fibers are a class of biomaterials that can be assembled using HIV-like kissing loop interactions. Because of the programmability of molecular design and low immunorecognition, these structures present an interesting opportunity to solve problems in nanobiotechnology and synthetic biology. However, the experimental tools to fully characterize and discriminate among different fiber structures in solution are limited. Herein, we utilize solid-state nanopore experiments and Brownian dynamics simulations to characterize and distinguish several RNA fiber structures that differ in their degrees of branching. We found that, regardless of the electrolyte type and concentration, fiber structures that have more branches produce longer and deeper ionic current blockades in comparison to the unbranched fibers. Experiments carried out at temperatures ranging from 20{\textendash}60 {\textdegree}C revealed almost identical distributions of current blockade amplitudes, suggesting that the kissing loop interactions in fibers are resistant to heating within this range.

}, issn = {2040-3364}, doi = {10.1039/D1NR08002D}, url = {http://pubs.rsc.org/en/content/articlepdf/2022/NR/D1NR08002D}, author = {Tripathi, Prabhat and Chandler, Morgan and Maffeo, Christopher Michael and Fallahi, Ali and Makhamreh, Amr and Halman, Justin and Aleksei Aksimentiev and Afonin, Kirill A. and Wanunu, Meni} } @article {362, title = {DNA Origami Voltage Sensors for Transmembrane Potentials with Single-Molecule Sensitivity}, journal = {Nano Letters}, volume = {21}, year = {2021}, month = {10/2021}, pages = {8634-8641}, chapter = {8634}, abstract = {

Signal transmission in neurons goes along with changes in the transmembrane potential. To report them, different approaches, including optical voltage-sensing dyes and genetically encoded voltage indicators, have evolved. Here, we present a DNA nanotechnology-based system and demonstrate its functionality on liposomes. Using DNA origami, we incorporated and optimized different properties such as membrane targeting and voltage sensing modularly. As a sensing unit, we used a hydrophobic red dye anchored to the membrane and an anionic green dye at the DNA to connect the nanostructure and the membrane dye anchor. Voltage-induced displacement of the anionic donor unit was read out by fluorescence resonance energy transfer (FRET) changes of single sensors attached to liposomes. A FRET change of \~{}5\% for ΔΨ = 100 mV was observed. The working mechanism of the sensor was rationalized by molecular dynamics simulations. Our approach holds potential for an application as nongenetically encoded membrane sensors.

}, doi = {10.1021/acs.nanolett.1c02584}, url = {https://pubs.acs.org/doi/10.1021/acs.nanolett.1c02584?fig=tgr1\&ref=pdf}, author = {Ochmann, Sarah E and Joshi, Himanshu and Büber, Ece and Franquelim, Henri G and Stegemann, Pierre and Sacc{\`a}, Barbara and Keyser, Ulrich F and Aleksei Aksimentiev and Tinnefeld, Philip} } @article {360, title = {Synthetic Macrocycle Nanopore for Potassium-Selective Transmembrane Transport}, journal = {Journal of the American Chemical Society}, volume = {143}, year = {2021}, month = {08/2021}, pages = {15975-15983}, chapter = {15975}, abstract = {

Reproducing the structure and function of biological membrane channels, synthetic nanopores have been developed for applications in membrane filtration technologies and biomolecular sensing. Stable stand-alone synthetic nanopores have been created from a variety of materials, including peptides, nucleic acids, synthetic polymers, and solid-state membranes. In contrast to biological nanopores, however, furnishing such synthetic nanopores with an atomically defined shape, including deliberate placement of each and every chemical group, remains a major challenge. Here, we introduce a chemosynthetic macromolecule,\ extended pillararene macrocycle (EPM) as a chemically defined transmembrane nanopore that exhibits selective transmembrane transport. Our ionic current measurements reveal stable insertion of individual EPM nanopores into a lipid bilayer membrane and remarkable cation type-selective transport, with up to a 21-fold selectivity for potassium over sodium ions. Taken together, direct chemical synthesis offers a path to de novo design of a new class of synthetic nanopores with custom transport functionality imprinted in their atomically defined chemical structure.\ 

}, keywords = {Electrical conductivity, MD Simulations, Nanopores, Potassium Ions Selectivity}, doi = {10.1021/jacs.1c04910}, author = {Qiao, Dan and Joshi, Himanshu and Zhu, Huangtianzhi and Wang, Fushi and Xu, Yang and Gao, Jia and Huang, Feihe and Aleksei Aksimentiev and Feng, Jiandong} } @article {356, title = {The emerging landscape of single-molecule protein sequencing technologies}, journal = {Nature Methods}, volume = {18}, year = {2021}, month = {06/2021}, chapter = {604-617}, abstract = {

Single-cell profiling methods have had a profound impact on the understanding of cellular heterogeneity. While genomes and transcriptomes can be explored at the single-cell level, single-cell profiling of proteomes is not yet established. Here we describe new single-molecule protein sequencing and identification technologies alongside innovations in mass spectrometry that will eventually enable broad sequence coverage in single-cell profiling. These technologies will in turn facilitate biological discovery and open new avenues for ultrasensitive disease diagnostics.

}, doi = {10.1038/s41592-021-01143-1}, url = {https://doi.org/10.1038/s41592-021-01143-1}, author = {Javier Antonio Alfaro and Peggy Bohl{\"a}nder and Mingjie Dai and Mike Filius and Cecil J. Howard and Xander F. van Kooten and Shilo Ohayon and Adam Pomorski and Sonja Schmid and Aleksei Aksimentiev and Eric V. Anslyn and Georges Bedran and Chan Cao and Mauro Chinappi and Etienne Coyaud and Cees Dekker and Gunnar Dittmar and Nicholas Drachman and Rienk Eelkema and David Goodlett and S{\'e}bastien Hentz and Umesh Kalathiya and Neil L. Kelleher and Ryan T. Kelly and Zvi Kelman and Sung Hyun Kim and Bernhard Kuster and David Rodriguez-Larrea and Stuart Lindsay and Giovanni Maglia and Edward M. Marcotte and John P. Marino and Christophe Masselon and Michael Mayer and Patroklos Samaras and Kumar Sarthak and Lusia Sepiashvili and Derek Stein and Meni Wanunu and Mathias Wilhelm and Peng Yin and Amit Meller and Chirlmin Joo} } @article {357, title = {A tetrahedral DNA nanorobot with conformational change in response to molecular trigger}, journal = {Nanoscale}, year = {2021}, month = {01/2021}, abstract = {

Dynamic DNA origami nanostructures that respond to external stimuli are promising platforms for cargo delivery and nanoscale sensing. However, the low stability of such nanostructures under physiological conditions presents a major obstacle for their use in biomedical applications. This article describes a stable tetrahedral DNA nanorobot (TDN) programmed to undergo a controlled conformational change in response to epithelial cell adhesion molecule (EpCAM), a molecular biomarker specifically expressed on the circulating tumor cells. Multiresolution molecular dynamics simulations verified the overall stability of the folded TDN design and characterized local distortions in the folded structure. Atomic force microscopy and gel electrophoresis results showed that tetragonal structures are more stable than unfolded DNA origami sheets. Live cell experiments demonstrated the low cytotoxicity and target specificity of TDN. In summary, the proposed TDN can not only effectively resist nuclease catalysis but also has the potential to monitor EpCAM-positive cells precisely.

}, issn = {2040-3364}, doi = {10.1039/D1NR02757C}, url = {http://xlink.rsc.org/?DOI=D1NR02757Chttp://pubs.rsc.org/en/content/articlepdf/2021/NR/D1NR02757Chttp://pubs.rsc.org/en/content/articlepdf/2021/NR/D1NR02757C}, author = {Liu, Fengyu and Liu, Xiaoming and Shi, Qing and Maffeo, Christopher and Kojima, Masaru and Dong, Lixin and Aleksei Aksimentiev and Huang, Qiang and Fukuda, Toshio and Arai, Tatsuo} } @article {335, title = {Scalable molecular dynamics on CPU and GPU architectures with NAMD}, journal = {J. Chem. Phys.}, volume = {153}, year = {2020}, month = {07/2020}, chapter = {044130}, abstract = {

NAMD is a molecular dynamics program designed for high-performance simulations of very large biological objects on CPU- and GPU- based architectures. NAMD offers scalable performance on petascale parallel supercomputers consisting of hundreds of thousands of cores, as well as on inexpensive commodity clusters commonly found in academic environments. It is written in C++ and leans on Charm++ parallel objects for optimal performance on low-latency architectures. NAMD is a versatile, multipurpose code that gathers state-of-the-art algorithms to carry out simulations in apt thermodynamic ensembles, using the widely popular CHARMM, AMBER, OPLS, and GROMOS biomolec- ular force fields. Here, we review the main features of NAMD that allow both equilibrium and enhanced-sampling molecular dynamics\ simulations with numerical efficiency. We describe the underlying concepts utilized by NAMD and their implementation, most notably for handling long-range electrostatics; controlling the temperature, pressure, and pH; applying external potentials on tailored grids; leveraging massively parallel resources in multiple-copy simulations; and hybrid quantum-mechanical/molecular-mechanical descriptions. We detail the variety of options offered by NAMD for enhanced-sampling simulations aimed at determining free-energy differences of either alchem- ical or geometrical transformations and outline their applicability to specific problems. Last, we discuss the roadmap for the development of NAMD and our current efforts toward achieving optimal performance on GPU-based architectures, for pushing back the limitations that have prevented biologically realistic billion-atom objects to be fruitfully simulated, and for making large-scale simulations less expensive and easier to set up, run, and analyze. NAMD is distributed free of charge with its source code at www.ks.uiuc.edu.

}, doi = {10.1063/5.0014475}, author = {James C. Phillips and David J. Hardy and Julio D. C. Maia and John E. Stone and Jo{\~a}o V. Ribeiro and Rafael C. Bernardi and Ronak Buch and Giacomo Fiorin and J{\'e}r{\^o}me H{\'e}nin and Wei Jiang and Ryan McGreevy and Marcelo C. R. Melo and Brian K. Radak and Robert D. Skeel and Abhishek Singharoy and Yi Wang and Beno{\^\i}t Roux and Aleksei Aksimentiev and Zaida Luthey-Schulten and Laxmikant V. Kal{\'e} and Klaus Schulten and Christophe Chipot and Emad Tajkhorshid} } @article {318, title = {Artificial Water Channels Enable Fast and Selective Water Permeation Through Water-wire Networks}, journal = {Nature Nanotechnology.}, volume = {15,}, year = {2020}, month = {01/2020}, pages = {73-79}, chapter = {73}, abstract = {

Artificial water channels are synthetic molecules that aim to mimic the structural and functional features of biological water channels (aquaporins). Here we report on a cluster-forming organic nanoarchitecture, peptide-appended hybrid[4]arene (PAH[4]), as a new class of artificial water channels. Fluorescence experiments and simulations demonstrated that PAH[4]s can form, through lateral diffusion, clusters in lipid membranes that provide synergistic membrane-spanning paths for rapid and selective water permeation through water-wire networks. Quantitative transport studies revealed that PAH[4]s can transport \>109\ water molecules per second per molecule, which is comparable to aquaporin water channels. The performance of these channels exceeds the upper bound limit of current desalination membranes by a factor of ~104, as illustrated by the water/NaCl permeability{\textendash}selectivity trade-off curve. PAH[4]{\textquoteright}s unique properties of a high water/solute permselectivity via cooperative water-wire formation could usher in an alternative design paradigm for permeable membrane materials in separations, energy production, and barrier applications.

}, doi = {https://doi.org/10.1038/s41565-019-0586-8}, author = {Woochul Song and Himanshu Joshi and Ratul Chowdhury and Joseph S. Najem and Yue-xiao Shen and Chao Lang and Codey B. Henderson and Yu-Ming Tu and Megan Farell and Megan E. Pitz and Costas D. Maranas and Paul S. Cremer and Robert J. Hickey and Stephen A. Sarles and Jun-li Hou and Aleksei Aksimentiev and Manish Kumar} } @article {319, title = {Rosette Nanotube Porins as Ion Selective Transporters and Single-Molecule Sensors}, journal = {Journal of the American Chemical Society}, volume = {142}, year = {2020}, month = {01/2020}, pages = {1680-1685}, chapter = {1680}, abstract = {

Rosette nanotubes (RNTs) are a class of materials formed by molecular self-assembly of a fused guanine-cytosine base (G^C base). An important feature of these self-assembled nanotubes is their precise atomic structure, intriguing for rational design and optimization as synthetic transmembrane porins. Here, we present experimental observations of ion transport across 1.1 nm inner diameter RNT porins (RNTPs) of various lengths in the range 5-200 nm. In a typical experiment, custom lipophilic RNTPs were first inserted into lipid vesicles; the vesicles then spontaneously fused with a planar lipid bilayer, which produced stepwise increases of ion current across the bilayer. Our measurements in 1 M KCl solution indicate ion transport rates of ~50 ions s-1 V-1 m, which for short channels amounts to conductance values of\  ~1 nS, commensurate with naturally occurring toxin channels such as α-hemolysin. Measurements of interaction times of α-cyclodextrin with RNTPs reveal two distinct unbinding time scales, which suggest that interactions of either face of α-cyclodextrin with the RNTP face are differentiable, backed with all-atom molecular dynamics simulations. Our results highlight the potential of RNTPs as self-assembled nonproteinaceous single-molecule sensors and selective nanofilters with tunable functionality through chemistry.

}, doi = {https://doi.org/10.1021/jacs.9b10993}, author = {Tripathi, Prabhat and Shuai, Liang and Joshi, Himanshu and Yamazaki, Hirohito and Fowle, William H and Aleksei Aksimentiev and Fenniri, Hicham and Wanunu, Meni} } @article {300, title = {Characterization of the Lipid Structure and Fluidity of Lipid Membranes on Epitaxial Graphene and Their Correlation to Graphene Features}, journal = {Langmuir}, volume = {35}, year = {2019}, month = {03/2019}, pages = {4726-4735}, abstract = {

Graphene has been recognized as an enhanced platform for biosensors because of its high electron mobility. To integrate active membrane proteins into graphene-based materials for such applications, graphene{\textquoteright}s surface must be functionalized with lipids to mimic the biological environment of these proteins. Several studies have examined supported lipids on various types of graphene and obtained conflicting results for the lipid structure. Here, we present a correlative characterization technique based on fluorescence measurements in a Raman spectroscopy setup to study the lipid structure and dynamics on epitaxial graphene. Compared to other graphene variations, epitaxial graphene is grown on a substrate more conducive to production of electronics and offers unique topographic features. On the basis of experimental and computational results, we propose that a lipid sesquilayer (1.5 bilayer) forms on epitaxial graphene and demonstrate that the distinct surface features of epitaxial graphene affect the structure and diffusion of supported lipids.

}, doi = {10.1021/acs.langmuir.9b00164}, url = {https://doi.org/10.1021/acs.langmuir.9b00164}, author = {Farell, Megan and Wetherington, Maxwell and Shankla, Manish and Chae, Inseok and Subramanian, Shruti and Kim, Seong H. and Aleksei Aksimentiev and Robinson, Joshua and Kumar, Manish} } @article {285, title = {Inchworm movement of two rings switching onto a thread by biased Brownian diffusion represent a three-body problem}, journal = {Proceedings of the National Academy of Sciences}, year = {2018}, month = {05/2018}, abstract = {

This article describes a molecular realization of the classical three-body problem, where the motion of three or more bodies is directed by a set of pairwise forces. Surprisingly, motion of the components of the three-body molecular systems is found to be highly choreographed by differences in strength of intercomponent interactions, promoting a rare inchworm-like loading of molecular rings onto a molecular thread. Our work demonstrates the utility of an integrative approach to design and develop functional molecular machines.The coordinated motion of many individual components underpins the operation of all machines. However, despite generations of experience in engineering, understanding the motion of three or more coupled components remains a challenge, known since the time of Newton as the {\textquotedblleft}three-body problem.{\textquotedblright} Here, we describe, quantify, and simulate a molecular three-body problem of threading two molecular rings onto a linear molecular thread. Specifically, we use voltage-triggered reduction of a tetrazine-based thread to capture two cyanostar macrocycles and form a [3]pseudorotaxane product. As a consequence of the noncovalent coupling between the cyanostar rings, we find the threading occurs by an unexpected and rare inchworm-like motion where one ring follows the other. The mechanism was derived from controls, analysis of cyclic voltammetry (CV) traces, and Brownian dynamics simulations. CVs from two noncovalently interacting rings match that of two covalently linked rings designed to thread via the inchworm pathway, and they deviate considerably from the CV of a macrocycle designed to thread via a stepwise pathway. Time-dependent electrochemistry provides estimates of rate constants for threading. Experimentally derived parameters (energy wells, barriers, diffusion coefficients) helped determine likely pathways of motion with rate-kinetics and Brownian dynamics simulations. Simulations verified intercomponent coupling could be separated into ring{\textendash}thread interactions for kinetics, and ring{\textendash}ring interactions for thermodynamics to reduce the three-body problem to a two-body one. Our findings provide a basis for high-throughput design of molecular machinery with multiple components undergoing coupled motion.

}, issn = {0027-8424}, doi = {10.1073/pnas.1719539115}, url = {http://www.pnas.org/content/early/2018/05/03/1719539115}, author = {Benson, Christopher R. and Maffeo, Christopher and Fatila, Elisabeth M. and Liu, Yun and Sheetz, Edward G. and Aleksei Aksimentiev and Singharoy, Abhishek and Flood, Amar H.} } @article {281, title = {Optical voltage sensing using DNA origami}, journal = {Nano Letters}, volume = {18}, year = {2018}, pages = {1962-1971}, abstract = {

We explore the potential of DNA nanotechnology for developing novel optical voltage sensing nano-devices that convert a local change of electric potential into optical signals. As a proof-of-concept of the sensing mechanism, we assembled voltage responsive DNA origami structures labelled with a single pair of FRET dyes. The DNA structures were reversibly immobilised on a nanocapillary tip and underwent controlled structural changes upon application of an electric field. The applied field was monitored through a change in FRET efficiency. By exchanging the position of a single dye, we could tune the voltage sensitivity of our DNA origami structure, demonstrating the flexibility and versatility of our approach. The experimental studies were complemented by coarse-grained simulations that characterised voltage-dependent elastic deformation of the DNA nanostructures and the associated change in the distance between the FRET pair. Our work opens a novel pathway for determining the mechanical properties of DNA origami structures, and highlights potential applications of dynamic DNA nanostructures as voltage sensors.

}, doi = {10.1021/acs.nanolett.7b05354}, url = {https://doi.org/10.1021/acs.nanolett.7b05354}, author = {Hemmig, Elisa Alina and Fitzgerald, Clare and Maffeo, Christopher and Hecker, Lisa and Ochmann, Sarah Elisabeth and Aleksei Aksimentiev and Tinnefeld, Philip and Keyser, Ulrich F} } @article {67, title = {The role of molecular modeling in bionanotechnology}, journal = {Phys Biol}, volume = {3}, year = {2006}, month = {2006 Mar}, pages = {S40-53}, abstract = {

Molecular modeling is advocated here as a key methodology for research and development in bionanotechnology. Molecular modeling provides nanoscale images at atomic and even electronic resolution, predicts the nanoscale interaction of unfamiliar combinations of biological and inorganic materials, and evaluates strategies for redesigning biopolymers for nanotechnological uses. The methodology is illustrated in this paper through reviewing three case studies. The first one involves the use of single-walled carbon nanotubes as biomedical sensors where a computationally efficient, yet accurate, description of the influence of biomolecules on nanotube electronic properties through nanotube-biomolecule interactions was developed; this development furnishes the ability to test nanotube electronic properties in realistic biological environments. The second case study involves the use of nanopores manufactured into electronic nanodevices based on silicon compounds for single molecule electrical recording, in particular, for DNA sequencing. Here, modeling combining classical molecular dynamics, material science and device physics, described the interaction of biopolymers, e.g., DNA, with silicon nitrate and silicon oxide pores, furnished accurate dynamic images of pore translocation processes, and predicted signals. The third case study involves the development of nanoscale lipid bilayers for the study of embedded membrane proteins and cholesterol. Molecular modeling tested scaffold proteins, redesigned apolipoproteins found in mammalian plasma that hold the discoidal membranes in the proper shape, and predicted the assembly as well as final structure of the nanodiscs. In entirely new technological areas such as bionanotechnology, qualitative concepts, pictures and suggestions are sorely needed; these three case studies document that molecular modeling can serve a critical role in this respect, even though it may still fall short on quantitative precision.

}, keywords = {Biosensing Techniques, Chemical Engineering, DNA, Lipid Bilayers, Membrane Potentials, Models, Molecular, Nanotechnology, Nanotubes, Carbon, Sequence Analysis, Silicon}, issn = {1478-3975}, doi = {10.1088/1478-3975/3/1/S05}, author = {Lu, Deyu and Aleksei Aksimentiev and Amy Y Shih and Eduardo Cruz-Ch{\'u} and Freddolino, Peter L and Arkhipov, Anton and Klaus Schulten} } @article {76, title = {Insights into the molecular mechanism of rotation in the Fo sector of ATP synthase}, journal = {Biophys J}, volume = {86}, year = {2004}, month = {2004 Mar}, pages = {1332-44}, abstract = {

F(1)F(o)-ATP synthase is a ubiquitous membrane protein complex that efficiently converts a cell{\textquoteright}s transmembrane proton gradient into chemical energy stored as ATP. The protein is made of two molecular motors, F(o) and F(1), which are coupled by a central stalk. The membrane unit, F(o), converts the transmembrane electrochemical potential into mechanical rotation of a rotor in F(o) and the physically connected central stalk. Based on available data of individual components, we have built an all-atom model of F(o) and investigated through molecular dynamics simulations and mathematical modeling the mechanism of torque generation in F(o). The mechanism that emerged generates the torque at the interface of the a- and c-subunits of F(o) through side groups aSer-206, aArg-210, and aAsn-214 of the a-subunit and side groups cAsp-61 of the c-subunits. The mechanism couples protonation/deprotonation of two cAsp-61 side groups, juxtaposed to the a-subunit at any moment in time, to rotations of individual c-subunit helices as well as rotation of the entire c-subunit. The aArg-210 side group orients the cAsp-61 side groups and, thereby, establishes proton transfer via aSer-206 and aAsn-214 to proton half-channels, while preventing direct proton transfer between the half-channels. A mathematical model proves the feasibility of torque generation by the stated mechanism against loads typical during ATP synthesis; the essential model characteristics, e.g., helix and subunit rotation and associated friction constants, have been tested and furnished by steered molecular dynamics simulations.

}, keywords = {Binding Sites, Cell Membrane, Computer Simulation, Dimerization, Models, Chemical, Models, Molecular, Models, Statistical, Molecular Motor Proteins, Protein Binding, Protein Conformation, Protein Subunits, Proton-Translocating ATPases, Rotation, Stochastic Processes}, issn = {0006-3495}, doi = {10.1016/S0006-3495(04)74205-8}, author = {Aleksei Aksimentiev and Ilya A Balabin and Fillingame, Robert H and Klaus Schulten} } @article {183, title = {Morphology of surfaces in mesoscopic polymers, surfactants, electrons, or reaction-diffusion systems: Methods, simulation and measurements}, journal = {Advances in Chemical Physics}, volume = {121}, year = {2002}, pages = {141{\textendash}239}, abstract = {

In this chapter the authors discuss systems with internal surfaces, ordered surfaces, topological transformations, and dynamical scaling. In Section II the authors show specific examples of mesoscopic systems with special attention devoted to the surfaces in the system{\textemdash}that is, periodic surfaces in surfactant systems, periodic surfaces in diblock copolymers, bicontinuous disordered interfaces in spinodally decomposing blends, ordered charge density wave patterns in electron liquids, and dissipative structures in reaction{\textendash}diffusion systems. Section III covers the theory of morphological measures, including the Euler characteristic and the Gaussian and mean curvatures.

}, doi = {10.1002/0471264318.ch3}, author = {Aleksei Aksimentiev and Robert Ho{\l}yst and Marcin Fialkowski} } @article {79, title = {Scaling of the Euler characteristic, surface area, and curvatures in the phase separating or ordering systems}, journal = {Phys Rev Lett}, volume = {86}, year = {2001}, month = {2001 Jan 8}, pages = {240-3}, abstract = {

We present robust scaling laws for the Euler characteristic and curvatures applicable to any symmetric system undergoing phase separating or ordering kinetics. We apply it to the phase ordering in a system of the nonconserved scalar order parameter and find three scaling regimes. The appearance of the preferred nonzero curvature of an interface separating +/- domains marks the crossover to the late stage regime characterized by the Lifshitz-Cahn-Allen scaling.

}, issn = {0031-9007}, author = {Marcin Fialkowski and Aleksei Aksimentiev and Robert Ho{\l}yst} }