Selective Capture and Manipulation of DNA through Double Charged Nanopores.

In the past few decades, nanometer-scale pores have been employed as powerful tools for sensing biological molecules. Owing to its unique structure and properties, solid-state nanopores provide interesting opportunities for the development of DNA sequencing technology. Controlling DNA translocation in nanopores is an important means of improving the accuracy of sequencing. Here we present a proof of principle study of accelerating DNA captured across targeted graphene nanopores using surface charge density and find the intrinsic mechanism of the combination of electroosmotic flow induced by charges of nanopore and electrostatic attraction/repulsion between the nanopore and ssDNA. The theoretical study performed here provides a new means for controlling DNA transport dynamics and makes better and cheaper application of graphene in molecular sequencing.

Actuation mechanism of a nanoscale drilling rig based on nested carbon nanotubes.

With the increasing emphasis on health and the continuous improvement of medical standards, more and more micro/nano devices are being used in the medical field. However, the existing micro/nano devices cannot effectively solve various problems encountered in medical processes and achieve specific therapeutic effects. Based on this, this article designs a new type of nanoscale drilling rig. The nanoscale drilling rig is composed of double-layer nested carbon nanotubes with multiple electrodes, and is powered by an external power source, making it easy to perform long-term surgery in the human body. Through coding strategies, we can adjust the surface charge density and distribution of the nanoscale drilling rig, thereby controlling its periodical rotation and achieving precise medical treatment. In addition, in order to control the length of the nanoscale drill bit, meet the treatment needs of different parts of the human body, and reduce damage to the human body, we have designed a structure of ion electric double layers so that the drill bit can be fixed in different positions, reducing the risk of treatment to a certain extent. This drilling rig enriches the functions of micro/nano devices, which is beneficial for the development of the medical industry.

Electroosmotic Sensing of Uncharged Peptides and Differentiating Their Phosphorylated States Using Nanopores.

The correct characterization and identification of different kinds of proteins is crucial for the survival and development of living organisms, and proteomics research promotes the analysis and understanding of future genome functions. Nanopore technique has been proved to accurately identify individual nucleotides. However, accurate and rapid protein sequencing is difficult due to the variability of protein structures that contains more than 20 amino acids, and it remains very challenging especially for uncharged peptides as they can not be electrophoretically driven through the nanopore. Graphene nanopores have the advantages of high accuracy, sensitivity and low cost in identifying protein phosphorylation modifications. Here, by using all-atom molecular dynamics simulations, charged graphene nanopores are employed to electroosmotically capture and sense uncharged peptides. By further mimicking AFM manipulation of single molecules, it is also found that the uncharged peptides and their phosphorylated states could also be differentiated by both the ionic current and pulling force signals during their pulling processes through the nanopore with a slow and constant velocity. The results shows ability of using nanopores to detect and discriminate single amino acid and its phosphorylation, which is essential for the future low-cost and high-throughput sequencing of protein residues and their post-translational modifications.

Strengthen oriented poly (L-lactic acid) monofilaments via mechanical training.

Polymer materials have found extensive applications in the clinical and medical domains due to their exceptional biocompatibility and biodegradability. Compared to metallic counterparts, polymers, particularly Poly (L-lactic acid) (PLLA), are more suitable for fabricating biodegradable stents. As a viscoelastic material, PLLA monofilaments exhibit a creep phenomenon under sustained tensile stress. This study explores the use of creep to enhance the mechanical attributes of PLLA monofilaments. By subjecting the highly oriented monofilaments to controlled, constant force stretching, we achieved notable improvements in their mechanical characteristics. The results, as confirmed by tensile testing and dynamic mechanical analysis, revealed a remarkable 67 % increase in total elongation and over a 20 % rise in storage modulus post-mechanical training. Further microscopic analyses, including Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM), revealed enhanced spacing and cavity formation. These mechanical advancements are attributed to the unraveling and a more orderly arrangement of molecular chains in the amorphous regions. This investigation offers a promising approach for augmenting the mechanical properties of PLLA monofilaments, potentially benefiting their application in biomedical engineering.

Modified Theoretical Model Predicts Radial Support Capacity of Polymer Braided Stents.

BACKGROUND AND OBJECTIVE: Self-expanding polymer braided stents are expected to replace metallic stents in the treatment of Peripheral Arterial Disease, which seriously endangers human health. To restore the patency of blocked peripheral arteries with different properties and functions, the radial supporting capacity of the stent should be considered corresponding to the vessel. A theoretical model can be established as an effective method to study the radial supporting capacity of the stent which can shorten the stent design cycle and realize the customization of the stent according to lesion site. However, the classical model developed by Jedwab and Clerc of radial force is only limited to metallic braided stents, and the predictions for polymer braided stents are deviated. METHODS: In this paper, based on the limitation of the J&C model for polymer braided stents, a modified radial force model for polymer braided stents was proposed, which considered the friction between monofilaments and the torsion of the monofilaments. And the modified model was verified by radial force tests of polymer braided stents with different structures and monofilaments. RESULTS: Compared with the J&C model, the proposed modified model has better predictability for the radial force of polymer braided stents that prepared with different braided structure and polymer monofilaments. The root mean squared error of modified model is 0.041±0.026, while that of the J&C model is 0.246±0.111. CONCLUSIONS: For polymer braided stents, the friction between the polymer monofilaments and the torsion of the monofilaments during the radial compression cannot be ignored. The radial force prediction accuracy of the modified model considering these factors was significantly improved. This work provides a research basis on the theoretical model of polymer braided stents, and improves the feasibility of rapid personalized customization of polymer braided stents.

Protein Deceleration and Sequencing Using Si3N4-CNT Hybrid Nanopores.

Protein sequencing is crucial for understanding the complex mechanisms driving biological functions and is of utmost importance in molecular diagnostics and medication development. Nanopores have become an effective tool for single molecule sensing, however, the weak charge and non-uniform charge distribution of protein make capturing and sensing very challenging, which poses a significant obstacle to the development of nanopore-based protein sequencing. In this study, to facilitate capturing of the unfolded protein, highly charged peptide was employed in our simulations, we found that the velocity of unfolded peptide translocating through a hybrid nanopore composed of silicon nitride membrane and carbon nanotube is much slower compared to bare silicon nitride nanopore, it is due to the significant interaction between amino acids and the surface of carbon nanotube. Moreover, by introducing variations in the charge states at the boundaries of carbon nanotube nanopores, the competition and combination of the electrophoretic and electroosmotic flows through the nanopores could be controlled, we then successfully regulated the translocation velocity of unfolded proteins through the hybrid nanopores. The proposed hybrid nanopore effectively retards the translocation velocity of protein through it, facilitates the acquisition of ample information for accurate amino acid identification.

Unfolding of protein using MoS2/SnS2heterostructure for nanopore-based sequencing.

Protein sequencing is crucial for understanding the complex mechanisms driving biological functions. However, proteins are usually folded in their native state and the mechanism of fast protein conformation transitions still remains unclear, which make protein sequencing challenging. Molecular dynamics simulations with accurate force field are now able to observe the entire folding/unfolding process, providing valuable insights into protein folding mechanisms. Given that proteins can be unfolded, nanopore technology shows great potential for protein sequencing. In this study, we proposed to use MoS2/SnS2heterostructures to firstly unfold proteins and then detect them by a nanopore in the heterostructural membrane. All-atom molecular dynamics simulations performed in this work provided rich atomic-level information for a comprehensive understanding of protein unfolding process and mechanism on the MoS2/SnS2heterostructure, it was found that the strong binding of protein to SnS2nanostripe and hydrogen bond breaking were the main reasons for unfolding the protein on the heterostructure. After the protein was fully unfolded, it was restrained on the nanostripe because of the affinity of protein to the SnS2nanostripe. Thus by integrating the proposed unfolding technique with nanopore technology, detection of linear unfolded peptide was realized in this work, allowing for the identification of protein components, which is essential for sequencing proteins in the near future.

Nanopore actuation of a DNA-tracked nanovehicle.

As a kind of nanomachine that has great potential for applications in nanoscale sensing and manipulation, nanovehicles with unique shapes and functions have received extensive attention in recent years. Different from the existing common method of using synthetic chemistry to design and manufacture a nanovehicle, here we theoretically report a molecularly assembled DNA-tracked nanovehicle that can move on a solid-state surface using molecular dynamics simulations. A graphene membrane with four nanopores acts as the chassis of the nanoscale vehicle, and two circular ssDNAs across the nanopores serve as the wheels. The electroosmotic flows induced by independently charged nanopores with different surface charge densities under external electric fields were found to be the main power to actuate the controlled rotary motion of circular ssDNAs across every two nanopores. By tuning the rotary speed of each circular ssDNA, the linear and turning movements of the designed nanovehicle were realized. The designed nanovehicle makes it possible to have access to almost everywhere in the human body, which would lead to significant breakthroughs in the fields of nanoscale surgery, drug delivery and so on. The research not only enriches the family of nanorobots, but also opens another way for designing nanovehicles.

Regulating mechanical performance of poly (l-lactide acid) stent by the combined effects of heat and aqueous media.

Annealing process has been applied to the development of thermoforming polymer braided stent and treating its basic constitute monofilaments, especially for Poly (l-lactide acid) (PLLA) condensed by lactic acid monomer made from the plant starch. In this work, high performance monofilaments were produced by melting spun and solid-state drawing methods. Inspired by the effects of water plasticization on semi-crystal polymer, PLLA monofilaments were annealed with and without constraint in vacuum and aqueous media. Then, the co-effects of water infestation and heat on the micro-structure and mechanical properties of these filaments were characterized. Furtherly, mechanical performance of PLLA braided stents shaped by different annealing methods was also compared. Results showed that annealing in aqueous media generated more obvious structure change of PLLA filaments. Interestingly, the combined effects of aqueous phase and thermal effectively increased the crystallinity, and decreased the molecular weight and orientation of PLLA filaments. Therefore, higher modulus, smaller strength, and elongation at the break for filaments could be obtained, which could furtherly realize better radial compression resistance of the braided stent. This annealing strategy could provide new perspectives between anneal and material properties of PLLA monofilaments, and provide more suitable manufacturing technics for polymer braided stent.

A controllable nanoscale telescopic arm designed by encoding the nested multi-walled carbon nanotubes.

Micro/nano manipulation technologies have shown enormous potential in the field of accurate surgery, which is expected to promote the development of precision medicine. Therefore, scientists have been devoted to designing and manipulating nanoscale devices and tools which can conduct surgical functions, such as penetration, drilling and cleaving targeting either single cells or biological tissues. To enrich the functionality of the family of nanomachines, a theoretical nanoscale telescopic arm manipulated by charge-tunable multi-walled carbon nanotubes is designed in this work. By using predesigned encoding strategies that could periodically alternate the external electric fields and surface charge densities of the nanorings embedded in the carbon nanotubes, well controlled manipulations of the telescopic arm are realized in MD simulations to mimic nanoscale surgeries. The telescopic arm can stretch out by the external electric force and draw back by vdW attraction between the nested nanotubes. Meanwhile, the electric double layer formed around the nanoring area in the nanotube is used as a brake during the retraction process to make the nanotube halt stably at the target position. The working distance could also be tuned by changing the number of the nested nanotubes, which presents a promising avenue for varieties of biomedical applications.

A hazardous boundary of Poly(L-lactic acid) braided stent design: Limited elastic deformability of polymer materials.

Poly (L-lactic acid) (PLLA) braided stents, which are expected to replace metal stents, are promising in peripheral vascular therapy due to their superior biocompatibility. Although various design ideas have been proposed and investigated on metal stents, few researches are related to the design theory of PLLA braided stent. In this article, mechanical performance of PLLA braided stents with different parameters was systematically evaluated, and a design theory based on material properties was proposed. Different from metal materials, the risk of filament deformation beyond elastic zone should be evaluated and controlled in PLLA stent design. The findings were obtained through combination study of experiments and simulations. Design parameters, including pitch angle and stent diameter, played a crucial role in mechanical performance of PLLA braided stent. The deformation of PLLA stents with larger pitch angles and stent diameters was in elastic zone and thus presented better mechanical performance with satisfactory resilience. This work could provide meaningful suggestions for preparing bioresorbable braided stents with suitable design parameters.

Key Factors of Mechanical Strength and Toughness in Oriented Poly(l-lactic acid) Monofilaments for a Bioresorbable Self-Expanding Stent.

The investigation of the strength and toughness of poly(l-lactic acid) (PLLA) monofilaments is essential as the fundamental element of a biodegradable braided stent. However, the determining factor remains poorly addressed with respect to influencing the mechanical behavior of PLLA monofilaments. In this work, the electron beam (EB) with different radiation doses was utilized to sterilize PLLA monofilaments. Properties of the monofilaments, including the breaking strength, elongation at break, molecular weight, orientation, and microstructure of the fracture, were characterized. Results showed that a random chain scission of PLLA resulting from EB during this process could cause the decrease in molecular weight, which led to the decline in breaking strength. Meanwhile, the irradiated monofilaments were found to have almost the same elongation at break below a dose of 30 kGy and declined by 71.41% up to a dose of 48 kGy. It was also found that the ductile fracture connection of the monofilament translated to the brittle fracture by comparing the microstructure without and with sterilization. These phenomena could originate from the destruction of the long molecular chains connecting the crystal plates into shorter ones by radiation. PLLA monofilaments with 0, 30, and 48 kGy were used to braid carotid stents. Compared with a carotid Wallstent, the PLLA stent can better provide radial supporting to the carotid lesion. This study provides preliminary experimental references to evaluate and predict the mechanical performance of PLLA braided stents.

Encoding Manipulation of DNA-Nanoparticle Assembled Nanorobot Using Independently Charged Array Nanopores.

During the past decades, scientists have developed different kinds of nanorobots based on various driving principles to realize controlled manipulation of them for potential applications like medical diagnosis and directed cargo delivery. In order to design a nanorobot with advantages of simple operation and precise control that can enrich the family of intelligent nanorobots, an encoding manipulation method is proposed to control the movement of a DNA-nanoparticle assembled nanorobot by combing electrophoresis and electroosmosis effect in independently charged array nanopores. The nanorobot is composed of one nanoparticle and one or two ssDNAs. ssDNAs act as the legs of the nanorobot. The selective ion transport through charged nanopores can induce cooperation and competition between the electroosmosis and electrophoresis, which is the main power to activate the nanorobot. Thus by simply switching the applied electric field and surface charge density of each nanopore which is defined as the encoded nanopore according to a predetermined strategy, the well-controlled encoding manipulation including capturing, releasing, jumping, and crawling of the nanorobot is realized in this work. The study is expected to realize its value in many interesting applications like drug delivery, nanosurgery, and so on in the near future.

Different properties of poly(L-lactic acid) monofilaments and its corresponding braided springs after constrained and unconstrained annealing.

Thermal annealing is widely applied to enhance the mechanical performance of PLLA monofilaments, which brings in a variety of expected strengths through different constrained methods. In this work, samples with constrained and unconstrained annealing process were both prepared and characterized, including mechanical performance, surface morphology, radial supporting performance and axial flexibility. Experimental results revealed that the monofilaments under constrained annealing showed higher elastic modulus with 6.4 GPa, which were higher than those without any constraint. While the maximal elongation at break with 51.11% were observed in unconstrained annealed monofilaments. Few changes were presented in the molecular weight between the two types of samples. Moreover, the springs under constrained annealing inhibited the most reliable radial supporting performance with higher radial compression force and chronic outward force, 0.665 N/mm and 0.14 N respectively. However, unconstrained annealing springs showed better flexibility with 0.178 N bending stiffness and 1.58 N maximum bending force. These results suggested that filaments and springs with various properties can be obtained under different annealing conditions.

Navigated Delivery of Peptide to the Nanopore Using In-Plane Heterostructures of MoS2 and SnS2 for Protein Sequencing.

The impressive success of DNA sequencing using nanopores makes it possible to realize nanopore based protein sequencing. Well-controlled capture and linear movement of the protein are essential for accurate nanopore protein sequencing. Here, by taking advantage of different binding affinities of protein to two isomorphic materials, we theoretically designed a heterostructual platform for delivering the unfolded peptide to the nanopore sensing region. Due to the stronger binding between the peptide and SnS2 compared to MoS2, the peptide would adsorb to the SnS2 nanostripe and keep its threadlike conformation in the MoS2/SnS2/MoS2 heterostructure. Through switching the direction of the applied electric field in real time, the peptide was strategically driven to move along the designed path to the target nanopore. The ionic current blockades were also found to be different as the compositions of the peptide were changed, indicating the possibility for differentiating different peptides using this platform.

Velocity control of protein translocation through a nanopore by tuning the fraction of benzenoid residues.

Protein sequencing is essential to unveil the mechanism of cellular processes that govern the function of living organisms, and which play a crucial role in the field of drug design and molecular diagnostics. Nanopores have been proved to be effective tools in single molecule sensing, but the fast translocation speed of a peptide through a nanopore is one of the major obstacles that hinders the development of nanopore-based protein sequencing. In this work, by using molecular dynamics simulations (MDS) it is found that the peptide containing more hydrophobic residues permeates slower through a molybdenum disulfide nanopore, which originates from the strong interaction between the membrane surface and the hydrophobic residues. The binding affinity is remarkable especially for benzenoid residues as they contain a hydrophobic aromatic ring that is composed of relatively non-polar C-C and C-H bonds. By tuning the fraction of benzenoid residues of the peptide, the velocity of the protein translocation through the nanopore is well controlled. The peptide with all the hydrophobic residues being benzenoid residues is found to translocate through the nanopore almost ten times slower than the one without any benzenoid residues, which is beneficial for gathering adequate information for precise amino acid identification.

A Nanoparticle-DNA Assembled Nanorobot Powered by Charge-Tunable Quad-Nanopore System.

Molecular machines hold keys to performing intrinsic functions in living cells so that the organisms can work properly, and unveiling the mechanism of functional molecule machines as well as elucidating the dynamic process of interaction with their surrounding environment is an attractive pharmaceutical target for human health. Due to the limitations of searching and exploring all possible motors in human bodies, designing and constructing functional nanorobots is vital for meeting the fast-rising demand of revealing life science and related diagnostics. Here, we theoretically designed a nanoparticle-DNA assembled nanorobot that can move along a solid-state membrane surface. The nanorobot is composed of a nanoparticle and four single-stranded DNAs. Our molecular dynamics simulations show that electroosmosis could be the main power driving the movement of a nanorobot. After the DNA strands were one-to-one captured by the nanopores in the membrane, by tuning the surface charge density of each nanopore, we have theoretically shown that the electroosmosis coupled with electrophoresis can be used to drive the movement of the nanorobot in desired directions along the graphene membrane surface. It is believed that the well-controlled nanorobot will lead to many exciting applications, such as cargo delivery, nanomanipulation, and so on, if it is implemented in the near future.

The effect of intrinsic characteristics on mechanical properties of poly(l-lactic acid) bioresorbable vascular stents.

Poly(L-lactic acid) (PLLA) is currently the bioresorbable polymer of choice for vascular stents with its superior biocompatibility and mechanical properties. However, it is still difficult to enhance the radial supporting capacity of PLLA stents without increasing the strut thickness. In this study, the performance of laser-cut thin-strut stents from two groups of PLLA tubes are investigated. We considered two groups of PLLA tubes. Group 1 indicates the longitudinally stretched from original 150-µm-thick tubes, and Group 2 indicates the directly thinned from original 150-µm-thick tubes. Three stages of mechanical tests were conducted in this study, which are defined as tensile tests of dog-bone specimens, radial loading tests of tubes and radial loading tests of stents. The results suggest that Group 2 has higher radial supporting capacity than Group 1 with the same wall thickness. This work serves as a basis for manufacturing thin-strut stents with sufficient radial supporting capacity.

Discrimination of Protein Amino Acid or Its Protonated State at Single-Residue Resolution by Graphene Nanopores.

The function of a protein is determined by the composition of amino acids and is essential to proteomics. However, protein sequencing remains challenging due to the protein's irregular charge state and its high-order structure. Here, a proof of principle study on the capability of protein sequencing by graphene nanopores integrated with atomic force microscopy is performed using molecular dynamics simulations. It is found that nanopores can discriminate a protein sequence and even its protonation state at single-residue resolution. Both the pulling forces and current blockades induced by the permeation of protein residues are found to be highly correlated with the type of amino acids, which makes the residues identifiable. It is also found that aside from the dimension, both the conformation and charge state of the residue can significantly influence the force and current signal during its permeation through the nanopore. In particular, due to the electro-osmotic flow effect, the blockade current for the double-protonated histidine is slightly smaller than that for single-protonated histidine, which makes it possible for discrimination of different protonation states of amino acids. The results reported here present a novel protein sequencing scheme using graphene nanopores combined with nanomanipulation technology.

Ionic current modulation from DNA translocation through nanopores under high ionic strength and concentration gradients.

Ion transport through nanopores is an important process in nature and has important engineering applications. To date, most studies of nanopore ion transport have been carried out with electrolytes of relatively low concentrations. In this paper, we report on ionic current modulation from the translocation of dsDNA through a nanopore under high ionic strength and with an electrolyte concentration gradient across the nanopore. Results show that in this case, DNA translocation can induce either negative or positive ionic current modulation, even though usually only downward peaks are expected under this high ion concentration. Through a series of experiments and numerical simulations with nanopores of different diameters and concentration gradients, it is found that the positive pulse is due to extra ions outside the electric double layer of the DNA that are brought into the nanopore by the enhanced electroosmotic flow (EOF) with the negatively charged DNA inside the nanopore.