Ashfaq Adnan

Atomistic simulation and measurement of pH dependent cancer therapeutic interactions with nanodiamond carrier

In this work, we have combined constant-pH molecular dynamics simulations and experiments to provide a quantitative analysis of pH dependent interactions between doxorubicin hydrochloride (DOX) cancer therapeutic and faceted nanodiamond (ND) nanoparticle carriers. Our study suggests that when a mixture of faceted ND and DOX is dissolved in a solvent, the pH of this solvent plays a controlling role in the adsorption of DOX molecules on the ND. We find that the binding of DOX molecules on ND occurs only at high pH and requires at least ∼10% of ND surface area to be fully titrated for binding to occur. As such, this study reveals important mechanistic insight underlying an ND-based pH-controlled therapeutic platform.

Enhancement of strength and stiffness of Nylon 6 filaments through carbon nanotubes reinforcement

We report a method to fabricate carbon nanotube reinforced Nylon filaments through an extrusion process. In this process, Nylon 6 and multiwalled carbon nanotubes (MWCNT) are first dry mixed and then extruded in the form of continuous filaments by a single screw extrusion method. Thermo gravimetric analysis (TGA) and differential scanning calorimetry (DSC) studies have indicated that there is a moderate increase in Tg without a discernible shift in the melting endotherm. Tensile tests on single filaments have demonstrated that Young’s modulus and strength of the nanophased filaments have increased by 220% and 164%, respectively with the addition of only 1wt.% MWCNTs. SEM studies and micromechanics based calculations have shown that the alignment of MWCNTs in the filaments, and high interfacial shear strength between the matrix and the nanotube reinforcement was responsible for such a dramatic improvement in properties.

MANUFACTURING AND CHARACTERIZATION OF CARBON NANOTUBE/POLYETHYLENE COMPOSITES

The present study describes a method to fabricate polymer matrix nanocomposites by reinforcing multi-walled carbon nanotubes through an extrusion process. Linear low density polyethylene (LLDPE) powder and multi-walled carbon nanotubes (CNTs) are first dry mixed and extruded in the form of filaments by a single screw extrusion process. After extrusion, the filament is partially cooled by chilled air, dried, and continuously wound in a spool. The filaments are then laid in roving, stacked in a unidirectional fashion, and consolidated in a compression molding machine to come up with laminated composites. Thermo gravimetric analysis (TGA) has been performed to compare the thermal stability of as-fabricated composites with the neat polymer. The TGA result shows that the extruded composites are thermally more stable than their neat counterparts. The crystalline nature of CNTs and of as-fabricated composites were identified by X-ray diffraction (XRD) studies. The XRD results indicate that the nanocomposite materials are more crystalline than the neat systems, and the differential scanning calorimetry studies also confirmed the same trend. The scanning electron microscopy result showed that the sizes of extruded neat and nanophased filaments were about 117 and 73 µm, respectively. Tensile coupons from the consolidated panels were then extracted both in longitudinal (0◦) and in transverse (90◦) directions and tested in a Minimat Tester. It was found that with the addition of 2% by weight of CNTs in LLDPE, the tensile strength and modulus of the composite has increased by about 34 and 38%, respectively. The (0◦ )a nd (90 ◦) coupons have also demonstrated that there are directional effects in the tensile response, which is believed to have been caused by the alignment of CNTs during the extrusion process. It is our understanding that such improvement in properties is because of the increase in crystallinity of the polymer due to CNT infusion, and also due to the alignment of CNTs in the extrusion direction in the nanocomposites.

3D Structural Integrity and Interactions of Single-Stranded Protein- Binding DNA in a Functionalized Nanopore

Biomarker-binding nucleotide sequences, like aptamers, have gained recent attention in cancer cell isolation and detection works. Self-assembly and 3D conformation of aptamers enable them to selectively capture and bind diseased cells and related biomarkers. One mode of utilizing such an extraordinary selective property of the aptamers is by grafting these in nanopores. Coating the inside walls of the nanopore with biomarker specific ligands, like DNA, changes the statistics of the dynamic translocation events. When the target protein passes through the nanopore, it interacts with ligand coated inside the nanopore, and the process alters the overall potential energy profile which is essentially specific to the protein detected. The fundamental goal in this process is to ensure that these detection motifs hold their structure and functionality under applied electric field and experimental conditions. We report here all-atom molecular dynamics simulations of the effects of external electric field on the 3D conformation of such DNA structures. The simulations demonstrate how the grafted moieties affect the translocation time, velocity, and detection frequency of the target molecule. We also investigated a novel case of protein translocation, where DNA is prebound to the protein. As model, a thrombin-specific G-quartet and thrombin pair was used for this study.

Effect of Shock-Induced Cavitation Bubble Collapse on the damage in the Simulated Perineuronal Net of the Brain

The purpose of this study is to conduct modeling and simulation to understand the effect of shock-induced mechanical loading, in the form of cavitation bubble collapse, on damage to the brain’s perineuronal nets (PNNs). It is known that high-energy implosion due to cavitation collapse is responsible for corrosion or surface damage in many mechanical devices. In this case, cavitation refers to the bubble created by pressure drop. The presence of a similar damage mechanism in biophysical systems has long being suspected but not well-explored. In this paper, we use reactive molecular dynamics (MD) to simulate the scenario of a shock wave induced cavitation collapse within the perineuronal net (PNN), which is the near-neuron domain of a brain’s extracellular matrix (ECM). Our model is focused on the damage in hyaluronan (HA), which is the main structural component of PNN. We have investigated the roles of cavitation bubble location, shockwave intensity and the size of a cavitation bubble on the structural evolution of PNN. Simulation results show that the localized supersonic water hammer created by an asymmetrical bubble collapse may break the hyaluronan. As such, the current study advances current knowledge and understanding of the connection between PNN damage and neurodegenerative disorders.

A study of mechanical behavior and morphology of carbon nanotube reinforced UHMWPE/Nylon 6 hybrid polymer nanocomposite fiber

We report a phenomenal increase in strength, modulus, and fracture strain of ultra high molecular weight polyethylene (UHMWPE) fiber by 103 %, 219 %, and 108 %, respectively through hybridizing this fiber with Nylon 6 as a minor phase and simultaneously reinforcing it with single-walled carbon nanotubes (SWCNTs). Loading of Nylon 6 and SWCNTs into UHMWPE was 20.0 wt% and 2.0 wt%, respectively. Hybridized fibers were processed using a solution spinning method coupled with melt mixing and extrusion. We claim that the enhancement in strain-to-failure of the nanocomposites is due to induced plasticity in the hybridized Nylon 6-UHMWPE polymers. The enhancement in strength and stiffness in the nanocomposites is attributed to the load sharing of the SWCNTs during deformation. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) studies showed that changes in percent crystallinity, rate of crystallization, crystallite size, alignment of nanotubes, sliding of polymer interfaces and strong adhesion of CNT/polymer blends were responsible for such enhancements.

Cavitation nucleation in gelatin: Experiment and mechanism

Dynamic cavitation in soft materials is becoming increasingly relevant due to emerging medical implications such as the potential of cavitation-induced brain injury or cavitation created by therapeutic medical devices. However, the current understanding of dynamic cavitation in soft materials is still very limited, mainly due to lack of robust experimental techniques. To experimentally characterize cavitation nucleation under dynamic loading, we utilize a recently developed experimental instrument, the integrated drop tower system. This technique allows quantitative measurements of the critical acceleration (acr) that corresponds to cavitation nucleation while concurrently visualizing time evolution of cavitation. Our experimental results reveal that acr increases with increasing concentration of gelatin in pure water. Interestingly, we have observed the distinctive transition from a sharp increase (pure water to 1% gelatin) to a much slower rate of increase (∼10× slower) between 1% and 7.5% gelatin. Theoretical cavitation criterion predicts the general trend of increasing acr, but fails to explain the transition rates. As a likely mechanism, we consider concentration-dependent material properties and non-spherical cavitation nucleation sites, represented by pre-existing bubbles in gels, due to possible interplay between gelatin molecules and nucleation sites. This analysis shows that cavitation nucleation is very sensitive to the initial configuration of a bubble, i.e., a non-spherical bubble can significantly increase acr. This conclusion matches well with the experimentally observed liquid-to-gel transition in the critical acceleration for cavitation nucleation. STATEMENT OF SIGNIFICANCE From a medical standpoint, understanding dynamic cavitation within soft materials, i.e., tissues, is important as there are both potential injury implications (blast-induced cavitation within the brain) as well as treatments utilizing the phenomena (lithotripsy). In this regard, the main results of the present work are (1) quantitative characterization of cavitation nucleation in gelatin samples as a function of gel concentration utilizing well-controlled mechanical impacts and (2) mechanistic understanding of complex coupling between cavitation and liquid-/solid-like material properties of gel. The new capabilities of testing soft gels, which can be tuned to mimic material properties of target organs, at high loading rate conditions and accurately predicting their cavitation behavior are an important step towards developing reliable cavitation criteria in the scope of their biomedical applications.

Damage and Failure of Axonal Microtubule under Extreme High Strain Rate: An In-Silico Molecular Dynamics Study

As a major cytoskeleton element of the axon, the breaking of microtubules (MTs) has been considered as a major cause of the axon degeneration. High strain rate loading is considered as one of the key factors in microtubule breaking. Due to the small size of microtubule, the real-time behavior of microtubule breaking is hard to capture. This study employs fully-atomistic molecular dynamics (MD) simulation to determine the failure modes of microtubule under different loadings conditions such as, unidirectional stretching, bending and hydrostatic expansion. For each loading conditions, MT is subjected to extreme high strain rate (108–109 s−1) loading. We argue that such level of high strain rate may be realized during cavitation bubble implosion. For each loading type, we have determined the critical energy for MT rupture. The associated rupture mechanisms are also discussed. We observed that the stretching has the lowest energy barrier to break the MT at the nanosecond time scale. Moreover, the breakage between the dimers starts at ~16% of total strain when stretched, which is much smaller compared to the reported strain-at-failure (50%) for lower strain rate loading. It suggests that MT fails at a significantly smaller strain states when loaded at higher strain rates.

On the atomistic-based continuum viscoelastic constitutive relations for axonal microtubules

Mechanical response of brains interior during traumatic brain injury is primarily governed by the cytoskeleton (CSK) and occurs over multiple length scales starting from the axonal substructure level. The axonal cytoskeleton can be viewed as a nanofiber reinforced nanocomposite structure where nano-fibrous microtubules (MTs) are arranged in staggered arrays and cross-linked by Tau proteins. Each MT is made of thirteen laterally connected protofilaments (PFs), each of which is formed via linear polymerization of αβ-heterodimer protein called tubulin. Recent studies suggest that the unique viscoelastic nature of axons governs the damage during traumatic brain injury. To understand how the internal substructures of axon influences the viscoelastic mechanical behavior of axon from a theoretical perspective, the viscoelastic properties of MTs need to be properly described. Since viscosity is a bulk property, the measurement methods are fairly consistent. On the other hand, the reported experimentally measured elastic properties of MTs vary by several orders of magnitude due to limitations of experimental tools. Alternatively, many have attempted to determine MT properties using theoretical and computational methods at different length scales ranging between the atomistic and the continuum level. The atomistic approaches capture the dynamics and interactions of a material at the atomic or atomic cluster level but these methods are computationally expensive and can model only a very small physical scale. On the other hand, the continuum theories lack finer scale details. Here, we present an atomistic-based continuum viscoelastic constitutive relation for microtubules (MTs) based on the interatomic potential for proteins and continuum homogenization method. The interaction potential includes both van der Waals and electrostatic interactions between the protein molecules. The calculated Youngs modulus of 3.385 GPa agrees reasonably well with the range of experimentally measured value without any parameter fitting. We have then investigated the viscoelastic response of MT based on the estimated viscosity using atomistic simulation and evaluated Youngs modulus using our method. The current theory suggests that MT behaves like a viscoelastic material when applied loading rate is extremely high, otherwise it acts like an elastic solid material.

Molecular Dynamics Study of Carbon Nanotube/Epoxy Interfaces Using ReaxFF

Typical electronics packages are assembled by integrating various parts on printed circuit boards (PCB). Traditional interconnect materials in electronics packages are not suitable for DoD electronics because in many DoD extremely transient conditions, mechanical failures of the whole packages invariably occur due to interconnect junction failures. The objective of the research is to computationally investigate the effect of high strain rate loadings on the thermal and mechanical damage/failure of carbon nanotube reinforced polymer nanocomposites. In pursuit of our research goal, we first seek to obtain the elastic properties of the nanocomposites. Properties at interface between CNT/polymer are critical to determine mechanical, electrical, and thermal properties of these nanocomosites. In the present study, we have used reactive force field (ReaxFF) to study the interfacial properties of CNT/EPON 862-DETDA nanocomposite system. Because molecular-level failure events can play a significant role in epoxy mechanical behavior, the ReaxFF can be used as an ideal tool for MD simulations involving crosslinked epoxies. Pull out simulations are performed to characterize the CNT/polymer interfacial interactions. Pull out energy is used to calculate the interfacial shear strength of CNT/polymer nanocomposite.