Atomistic numerical investigation of single-crystal copper nanowire with surface defects

Based on the embedded atom method (EAM), a molecular dynamics (MD) simulation is performed to study the single-crystal copper nanowire with surface defects through tension. The tension simulations for nanowire without defect are first carried out under different temperatures, strain rates and time steps and then surface defect effects for nanowire are investigated. The stress-strain curves obtained by the MD simulations of various strain rates show a rate below 1 x 10(9) s-1 will exert less effect on the yield strength and yield point, and the Young's modulus is independent of strain rate. a time step below 5 fs is recommend for the atomic model during the MD simulation. It is observed that high temperature leads to low Young's modulus, as well as the yield strength. The surface defects on nanowires are systematically studied in considering different defect orientations. It is found that the surface defect serves as a dislocation source, and the yield strength shows 34.20% decresse with 45 degree surface defect. Both yield strength and yield point are significantly influenced by the surface defects, except the Young's modulus.

Exploration of the defect’s effect on the mechanical properties of different orientated nanowires

Molecular dynamics (MD) simulations have been carried out to investigate the defect’s effect on the mechanical properties of copper nanowire with different crystallographic orientations, under tensile deformation. Three different crystallographic orientations have been considered. The deformation mechanism has been carefully discussed. It is found that the Young’s modulus is insensitive to the defect, even when the nanowire’s crystallographic orientation is different. However, due to the defect’s effect, the yield strength and yield strain appear a large decrease. The defects have played a role of dislocation sources, the slips or stacking faults are first generated around the locations of the defects. The necking locations have also been affected by different defects. Due to the surface defect, the plastic deformation has received a large influence for the <001>/{110} and <110> orientated nanowires, and a relative small influence is seen for the <111> nanowire.

Numerical exploration of plastic deformation mechanisms of copper nanowires with surface defects

Based on the molecular dynamics simulation, plastic deformation mechanisms associated with the zigzag stress curves in perfect and surface defected copper nanowires under uniaxial tension are studied. In our previous study, it has found that the surface defect exerts larger influence than the centro-plane defect, and the 45o surface defect appears as the most influential surface defect. Hence, in this paper, the nanowire with a 45o surface defect is chosen to investigate the defect’s effect to the plastic deformation mechanism of nanowires. We find that during the plastic deformation of both perfect and defected nanowires, decrease regions of the stress curve are accompanied with stacking faults generation and migration activities, but during stress increase, the structure of the nanowire appears almost unchanged. We also observe that surface defects have obvious influence on the nanowire’s plastic deformation mechanisms. In particular, only two sets of slip planes are found to be active and twins are also observed in the defected nanowire.

Advanced numerical characterization of mono-crystalline copper with defects

Based on the embedded atom method (EAM) and molecular dynamics (MD) method, the mono-crystalline copper with different defects is investigated through tension and nanoindentation simulation. The single-crystal copper nanowire with surface defects is firstly studied through tension. For validation, the tension simulations for nanowire without defect are carried out under different temperatures and strain rates. The defects on nanowires are then systematically studied in considering different defects orientation distribution. It is found that the Young’s modulus is insensitive of surface defects and centro-plane defects. However, the yield strength and yield point show a significant decrease due to the different defects. Specially, the 〖45〗^° defect in surface and in (200) plane exerts the biggest influence to the yield strength, about 34.20% and 51.45% decrease are observed, respectively. Different defects are observed to serve as a dislocation source and different necking positions of the nanowires during tension are found. During nanoindentation simulation, dislocation is found nucleating below the contact area, but no obvious dislocation is generated around the nano-cavity. Comparing with the perfect substrate during nanoindentation, the substrate with nano-cavities emerged less dislocations, it is supposed that the nano-cavity absorbed part of the indent energy, and less plastic deformation happened in the defected substrate.

Numerical exploration of the defect’s effect on mechanical properties of nanowires under torsion

Molecular dynamics (MD) simulations have been carried out to investigate the defect’s effect on the mechanical properties of single-crystal copper nanowire with different surface defects, under torsion deformation. The torsional rigidity is found insensitive to the surface defects and the critical angle appears an obvious decrease due to the surface defects, the largest decrease is found for the nanowire with surface horizon defect. The deformation mechanism appears different degrees of influence due to surface defects. The surface defects play a role of dislocation sources. Comparing with single intrinsic stacking faults formation for the perfect nanowire, much affluent deformation processes have been activated because of surface defects, for instance, we find the twins formation for the nanowire with a surface 45o defect.

Atomistic exploration of deformation properties of copper nanowires with pre-existing defects

Based on the embedded atom method (EAM) and molecular dynamics (MD) method, in this paper, the tensile deformation properties of Cu nanowires (NWs) with different pre-existing defects, including single surface defects, surface bi-defects and single internal defects, are systematically studied. In-depth deformation mechanisms of NWs with pre-existing defects are also explored. It is found that Young's modulus is insensitive to different pre-existing defects, but yield strength shows an obvious decrease. Defects are observed influencing greatly on NWs' tensile deformation mechanisms, and playing a role of dislocation sources. Besides of the traditional deformation process dominated by the nucleation and propagation of partial dislocations, the generations of twins, grain boundaries, fivefold deformation twins, hexagonal close-packed (HCP) structure and phase transformation from face-centred cubic (FCC) structure to HCP structure have been triggered by pre-existing defects. It is found that surface defect intends to induce larger influence to yield strength than internal defect. Most importantly, the defect that lies on slip planes exerts larger influence than other defects. As expected, it is also found that the more or longer of the defect, the bigger influence will be induced.

Theoretical and numerical investigation of bending properties of Cu nanowires

Based on the AFM-bending experiments, a molecular dynamics (MD) bending simulation model is established which could accurately account for the full spectrum of the mechanical properties of NWs in a double clamped beam configuration, ranging from elasticity to plasticity and failure. It is found that, loading rate exerts significant influence to the mechanical behaviours of nanowires (NWs). Specifically, a loading rate lower than 10 m/s is found reasonable for a homogonous bending deformation. Both loading rate and potential between the tip and the NW are found to play an important role in the adhesive phenomenon. The force versus displacement (F-d) curve from MD simulation is highly consistent in shapes with that from experiments. Symmetrical F-d curves during loading and unloading processes are observed, which reveal the linear-elastic and non-elastic bending deformation of NWs. The typical bending induced tensile-compressive features are observed. Meanwhile, the simulation results are excellently fitted by the classical Euler-Bernoulli beam theory with axial effect. It is concluded that, axial tensile force becomes crucial in bending deformation when the beam size is down to nanoscale for double clamped NWs. In addition, we find shorter NWs will have an earlier yielding and a larger yielding force. Mechanical properties (Young’s modulus & yield strength) obtained from both bending and tensile deformations are found comparable with each other. Specifically, the modulus is essentially similar under these two loading methods, while the yield strength during bending is observed larger than that during tension.

Rational design of serine protease inhibitors

Proteases regulate a spectrum of diverse physiological processes, and dysregulation of proteolytic activity drives a plethora of pathological conditions. Understanding protease function is essential to appreciating many aspects of normal physiology and progression of disease. Consequently, development of potent and specific inhibitors of proteolytic enzymes is vital to provide tools for the dissection of protease function in biological systems and for the treatment of diseases linked to aberrant proteolytic activity. The studies in this thesis describe the rational design of potent inhibitors of three proteases that are implicated in disease development. Additionally, key features of the interaction of proteases and their cognate inhibitors or substrates are analysed and a series of rational inhibitor design principles are expounded and tested. Rational design of protease inhibitors relies on a comprehensive understanding of protease structure and biochemistry. Analysis of known protease cleavage sites in proteins and peptides is a commonly used source of such information. However, model peptide substrate and protein sequences have widely differing levels of backbone constraint and hence can adopt highly divergent structures when binding to a protease’s active site. This may result in identical sequences in peptides and proteins having different conformations and diverse spatial distribution of amino acid functionalities. Regardless of this, protein and peptide cleavage sites are often regarded as being equivalent. One of the key findings in the following studies is a definitive demonstration of the lack of equivalence between these two classes of substrate and invalidation of the common practice of using the sequences of model peptide substrates to predict cleavage of proteins in vivo. Another important feature for protease substrate recognition is subsite cooperativity. This type of cooperativity is commonly referred to as protease or substrate binding subsite cooperativity and is distinct from allosteric cooperativity, where binding of a molecule distant from the protease active site affects the binding affinity of a substrate. Subsite cooperativity may be intramolecular where neighbouring residues in substrates are interacting, affecting the scissile bond’s susceptibility to protease cleavage. Subsite cooperativity can also be intermolecular where a particular residue’s contribution to binding affinity changes depending on the identity of neighbouring amino acids. Although numerous studies have identified subsite cooperativity effects, these findings are frequently ignored in investigations probing subsite selectivity by screening against diverse combinatorial libraries of peptides (positional scanning synthetic combinatorial library; PS-SCL). This strategy for determining cleavage specificity relies on the averaged rates of hydrolysis for an uncharacterised ensemble of peptide sequences, as opposed to the defined rate of hydrolysis of a known specific substrate. Further, since PS-SCL screens probe the preference of the various protease subsites independently, this method is inherently unable to detect subsite cooperativity. However, mean hydrolysis rates from PS-SCL screens are often interpreted as being comparable to those produced by single peptide cleavages. Before this study no large systematic evaluation had been made to determine the level of correlation between protease selectivity as predicted by screening against a library of combinatorial peptides and cleavage of individual peptides. This subject is specifically explored in the studies described here. In order to establish whether PS-SCL screens could accurately determine the substrate preferences of proteases, a systematic comparison of data from PS-SCLs with libraries containing individually synthesised peptides (sparse matrix library; SML) was carried out. These SML libraries were designed to include all possible sequence combinations of the residues that were suggested to be preferred by a protease using the PS-SCL method. SML screening against the three serine proteases kallikrein 4 (KLK4), kallikrein 14 (KLK14) and plasmin revealed highly preferred peptide substrates that could not have been deduced by PS-SCL screening alone. Comparing protease subsite preference profiles from screens of the two types of peptide libraries showed that the most preferred substrates were not detected by PS SCL screening as a consequence of intermolecular cooperativity being negated by the very nature of PS SCL screening. Sequences that are highly favoured as result of intermolecular cooperativity achieve optimal protease subsite occupancy, and thereby interact with very specific determinants of the protease. Identifying these substrate sequences is important since they may be used to produce potent and selective inhibitors of protolytic enzymes. This study found that highly favoured substrate sequences that relied on intermolecular cooperativity allowed for the production of potent inhibitors of KLK4, KLK14 and plasmin. Peptide aldehydes based on preferred plasmin sequences produced high affinity transition state analogue inhibitors for this protease. The most potent of these maintained specificity over plasma kallikrein (known to have a very similar substrate preference to plasmin). Furthermore, the efficiency of this inhibitor in blocking fibrinolysis in vitro was comparable to aprotinin, which previously saw clinical use to reduce perioperative bleeding. One substrate sequence particularly favoured by KLK4 was substituted into the 14 amino acid, circular sunflower trypsin inhibitor (SFTI). This resulted in a highly potent and selective inhibitor (SFTI-FCQR) which attenuated protease activated receptor signalling by KLK4 in vitro. Moreover, SFTI-FCQR and paclitaxel synergistically reduced growth of ovarian cancer cells in vitro, making this inhibitor a lead compound for further therapeutic development. Similar incorporation of a preferred KLK14 amino acid sequence into the SFTI scaffold produced a potent inhibitor for this protease. However, the conformationally constrained SFTI backbone enforced a different intramolecular cooperativity, which masked a KLK14 specific determinant. As a consequence, the level of selectivity achievable was lower than that found for the KLK4 inhibitor. Standard mechanism inhibitors such as SFTI rely on a stable acyl-enzyme intermediate for high affinity binding. This is achieved by a conformationally constrained canonical binding loop that allows for reformation of the scissile peptide bond after cleavage. Amino acid substitutions within the inhibitor to target a particular protease may compromise structural determinants that support the rigidity of the binding loop and thereby prevent the engineered inhibitor reaching its full potential. An in silico analysis was carried out to examine the potential for further improvements to the potency and selectivity of the SFTI-based KLK4 and KLK14 inhibitors. Molecular dynamics simulations suggested that the substitutions within SFTI required to target KLK4 and KLK14 had compromised the intramolecular hydrogen bond network of the inhibitor and caused a concomitant loss of binding loop stability. Furthermore in silico amino acid substitution revealed a consistent correlation between a higher frequency of formation and the number of internal hydrogen bonds of SFTI-variants and lower inhibition constants. These predictions allowed for the production of second generation inhibitors with enhanced binding affinity toward both targets and highlight the importance of considering intramolecular cooperativity effects when engineering proteins or circular peptides to target proteases. The findings from this study show that although PS-SCLs are a useful tool for high throughput screening of approximate protease preference, later refinement by SML screening is needed to reveal optimal subsite occupancy due to cooperativity in substrate recognition. This investigation has also demonstrated the importance of maintaining structural determinants of backbone constraint and conformation when engineering standard mechanism inhibitors for new targets. Combined these results show that backbone conformation and amino acid cooperativity have more prominent roles than previously appreciated in determining substrate/inhibitor specificity and binding affinity. The three key inhibitors designed during this investigation are now being developed as lead compounds for cancer chemotherapy, control of fibrinolysis and cosmeceutical applications. These compounds form the basis of a portfolio of intellectual property which will be further developed in the coming years.

Polymer self assembly on carbon nanotubes

This chapter analyses the poly(3-hexylthiophene) self-assembly on carbon nanotubes and the interaction between the two materials forming a new hybrid nanostructure. The chapter starts with a review of the several studies investigating polymers and biomolecules self-assembled on nanotubes. Then conducting polymers and polythiophenes are briefly introduced. Accordingly, carbon nanotube structure and properties are reported in Sect. 3. The experimental section starts with the bulk characterisation of polymer thin films with the inclusion of uniformly distributed carbon nanotubes. By using volume film analysis techniques (AFM, TEM, UV–Vis and Raman), we show how the polymer’s higher degree of order is a direct consequence of interaction with carbon nanotubes. Nevertheless, it is through the use of nanoscale analysis and molecular dynamic simulations that the self-assembly of the polymer on the nanotube surface can be clearly evidenced and characterised. In Sect. 6, the effect of the carbon templating structure on the P3HT organisation on the surface is investigated, showing the chirality-driven polymer assembly on the carbon nanotube surface. The interaction between P3HT and CNTs brings also to charge transfer, with the modification of physical properties for both species. In particular, the alteration of the polymer electronic properties and the modification of the nanotube mechanical structure are a direct consequence of the P3HT p-p stacking on the nanotube surface. Finally, some considerations based on molecular dynamics studies are reported in order to confirm and support the experimental results discussed.

Modified beam theories for bending properties of nanowires considering surface/intrinsic effects and axial extension effect

Several studies of the surface effect on bending properties of a nanowire (NW) have been conducted. However, these analyses are mainly based on theoretical predictions, and there is seldom integration study in combination between theoretical predictions and simulation results. Thus, based on the molecular dynamics (MD) simulation and different modified beam theories, a comprehensive theoretical and numerical study for bending properties of nanowires considering surface/intrinsic stress effects and axial extension effect is conducted in this work. The discussion begins from the Euler-Bernoulli beam theory and Timoshenko beam theory augmented with surface effect. It is found that when the NW possesses a relatively small cross-sectional size, these two theories cannot accurately interpret the true surface effect. The incorporation of axial extension effect into Euler-Bernoulli beam theory provides a nonlinear solution that agrees with the nonlinear-elastic experimental and MD results. However, it is still found inaccurate when the NW cross-sectional size is relatively small. Such inaccuracy is also observed for the Euler-Bernoulli beam theory augmented with both contributions from surface effect and axial extension effect. A comprehensive model for completely considering influences from surface stress, intrinsic stress, and axial extension is then proposed, which leads to good agreement with MD simulation results. It is thus concluded that, for NWs with a relatively small cross-sectional size, a simple consideration of surface stress effect is inappropriate, and a comprehensive consideration of the intrinsic stress effect is required.

MD investigations for mechanical properties of copper nanowires with and without surface defects

Based on the molecular dynamics (MD) method, the single-crystalline copper nanowire with different surface defects is investigated through tension simulation. For comparison, the MD tension simulations of perfect nanowire are firstly carried out under different temperatures, strain rates, and sizes. It has concluded that the surface-volume ratio significantly affects the mechanical properties of nanowire. The surface defects on nanowires are then systematically studied in considering different defect orientation and distribution. It is found that the Young’s modulus is insensitive of surface defects. However, the yield strength and yield point show a significant decrease due to the different defects. Different defects are observed to serve as a dislocation source.

A fundamental numerical and theoretical study for the vibrational properties of nanowires

Based on the molecular dynamics (MD) simulation and the classical Euler-Bernoulli beam theory, a fundamental study of the vibrational performance of the Ag nanowire (NW) is carried out. A comprehensive analysis of the quality (Q)-factor, natural frequency, beat vibration, as well as high vibration mode is presented. Two excitation approaches, i.e., velocity excitation and displacement excitation, have been successfully implemented to achieve the vibration of NWs. Upon these two kinds of excitations, consistent results are obtained, i.e., the increase of the initial excitation amplitude will lead to a decrease to the Q-factor, and moderate plastic deformation could increase the first natural frequency. Meanwhile, the beat vibration driven by a single relatively large excitation or two uniform excitations in both two lateral directions is observed. It is concluded that the nonlinear changing trend of external energy magnitude does not necessarily mean a nonconstant Q-factor. In particular, the first order natural frequency of the Ag NW is observed to decrease with the increase of temperature. Furthermore, comparing with the predictions by Euler- Bernoulli beam theory, the MD simulation provides a larger and smaller first vibration frequencies for the clamped-clamped and clamped-free thin Ag NWs, respectively. Additionally, for thin NWs, the first order natural frequency exhibits a parabolic relationship with the excitation magnitudes. The frequencies of the higher vibration modes tend to be low in comparison to Euler-Bernoulli beam theory predictions. A combined initial excitation is proposed which is capable to drive the NW under a multi-mode vibration and arrows the coexistence of all the following low vibration modes. This work sheds lights on the better understanding of the mechanical properties of NWs and benefits the increasing utilities of NWs in diverse nano-electronic devices.