## ASU Electronic Theses and Dissertations

This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.

In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.

Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.

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2011 2019

## Recent Submissions

Solid tumors advance from benign stage to a deadly metastatic state due to the complex interaction between cancer cells and tumor microenvironment (TME) including stromal cells and extracellular matrix (ECM). Multiple studies have demonstrated that ECM dysregulation is one of the critical hallmarks of cancer progression leading to formation of a desmoplastic microenvironment that participates in tumor progression. Cancer associated fibroblasts (CAFs) are the predominant stromal cell type that participates in desmoplasia by depositing matrix proteins and increasing ECM stiffness. Although the influence of matrix stiffness on enhanced tumorigenicity has been well studied, the biological understanding about the dynamic changes …

Contributors
Saini, Harpinder, Nikkhah, Mehdi, Ros, Robert, et al.
Created Date
2019

Calcitonin Gene-Related Peptide (CGRP) is an intrinsically disordered protein that has no regular secondary structure, but plays an important role in vasodilation and pain transmission in migraine. Little is known about the structure and dynamics of the monomeric state of CGRP or how CGRP is able to function in the cell, despite the lack of regular secondary structure. This work focuses characterizing the non-local structural and dynamical properties of the CGRP monomer in solution, and understanding how these are affected by the sequence and the solution environment. The unbound, free state of CGRP is measured using a nanosecond laser-pump spectrophotometer, …

Contributors
Sizemore, Sara, Vaiana, Sara, Ghirlanda, Giovanna, et al.
Created Date
2015

CpG methylation is an essential requirement for the normal development of mammals, but aberrant changes in the methylation can lead to tumor progression and cancer. An in-depth understanding of this phenomenon can provide insights into the mechanism of gene repression. We present a study comparing methylated DNA and normal DNA wrt its persistence length and contour length. Although, previous experiments and studies show no difference between the physical properties of the two, the data collected and interpreted here gives a different picture to the methylation phenomena and its effect on gene silencing. The study was extended to the artificially reconstituted …

Contributors
Kaur, Parminder, Lindsay, Stuart, Ros, Robert, et al.
Created Date
2012

Single molecule identification is one essential application area of nanotechnology. The application areas including DNA sequencing, peptide sequencing, early disease detection and other industrial applications such as quantitative and quantitative analysis of impurities, etc. The recognition tunneling technique we have developed shows that after functionalization of the probe and substrate of a conventional Scanning Tunneling Microscope with recognition molecules ("tethered molecule-pair" configuration), analyte molecules trapped in the gap that is formed by probe and substrate will bond with the reagent molecules. The stochastic bond formation/breakage fluctuations give insight into the nature of the intermolecular bonding at a single molecule-pair level. …

Contributors
Zhao, Yanan, Lindsay, Stuart, Nemanich, Robert, et al.
Created Date
2014

Cancer is a serious health concern. Current treatments are limited due to certain subpopulations of cancer cells being resistant to chemotherapy and radiation. These subpopulations have been qualitatively identified but much work remains to quantify the abnormalities they exhibit such as irregular nuclear shape. This dissertation seeks to determine physical science methods which can identify and quantify the biological characteristics of cancer and non-cancer cells. For the first project, the deoxyribonucleic acid (DNA) and chromatin of cancer and non-cancer esophageal cells were quantified using spectrophotometry and atomic force microscopy. Then the cellular nucleus shape, chromocenters, nucleoli, and nuclear speckles were …

Contributors
ARIYASINGHE, NETHMI KANCHANA, Ros, Robert, Arizona State University
Created Date
2019

Mechanical properties, in particular elasticity, of cancer cells and their microenvironment are important in governing cancer cell fate, for example function, mobility, adhesion, and invasion. Among all tools to measure the mechanical properties, the precision and ease of atomic force microscopy (AFM) to directly apply force—in the range of Pico to micronewtons—onto samples—with length scales from nanometers to tens of micrometers—has made it a powerful tool to investigate the mechanics of materials. AFM is widely used to measure deformability and stiffness of soft biological samples. Principally, these samples are indented by the AFM probe and the forces and indentation depths …

Contributors
Rahmani Eliato, Kiarash, Ros, Robert, Nikkhah, Mehdi, et al.
Created Date
2019

Nanofluidic devices in which one single-walled carbon nanotube (SWCNT) spans a barrier between two fluid reservoirs were constructed, enabling direct electrical measurement of the transport of ions and molecules. Ion current through these devices is about 2 orders of magnitude larger than that predicted from the bulk resistivity of the electrolyte. Electroosmosis drives excess current, carried by cations, and is found to be the origin of giant ionic current through SWCNT as shown by building an ionic field-effect transistor with a gate electrode embedded in the fluid barrier. Wetting of inside of the semi-conducting SWCNT by water showed the change …

Contributors
Pang, Pei, Lindsay, Stuart, Ros, Robert, et al.
Created Date
2011

An animal's ability to produce protein-based silk materials has evolved independently in many different arthropod lineages, satisfying various ecological necessities. However, regardless of their wide range of uses and their potential industrial and biomedical applications, advanced knowledge on the molecular structure of silk biopolymers is largely limited to those produced by spiders (order Araneae) and silkworms (order Lepidoptera). This thesis provides an in-depth molecular-level characterization of silk fibers produced by two vastly different insects: the caddisfly larvae (order Trichoptera) and the webspinner (order Embioptera). The molecular structure of caddisfly larval silk from the species <italic>Hesperophylax consimilis</italic> was characterized using solid-state …

Contributors
Addison, John Bennett, Yarger, Jeffery L, Holland, Gregory P, et al.
Created Date
2014

Single molecules in a tunnel junction can now be interrogated reliably using chemically-functionalized electrodes. Monitoring stochastic bonding fluctuations between a ligand bound to one electrode and its target bound to a second electrode ("tethered molecule-pair" configuration) gives insight into the nature of the intermolecular bonding at a single molecule-pair level, and defines the requirements for reproducible tunneling data. Importantly, at large tunnel gaps, there exists a regime for many molecules in which the tunneling is influenced more by the chemical identity of the molecules than by variability in the molecule-metal contact. Functionalizing a pair of electrodes with recognition reagents (the …

Contributors
Chang, Shuai, Lindsay, Stuart, Ros, Robert, et al.
Created Date
2012

This thesis describes several experiments based on carbon nanotube nanofludic devices and field-effect transistors. The first experiment detected ion and molecule translocation through one single-walled carbon nanotube (SWCNT) that spans a barrier between two fluid reservoirs. The electrical ionic current is measured. Translocation of small single stranded DNA oligomers is marked by large transient increases in current through the tube and confirmed by a PCR (polymerase chain reaction) analysis. Carbon nanotubes simplify the construction of nanopores, permit new types of electrical measurement, and open new avenues for control of DNA translocation. The second experiment constructed devices in which the interior …

Contributors
Cao, Di, Lindsay, Stuart, Vaiana, Sara, et al.
Created Date
2011

Richard Feynman said “There’s plenty of room at the bottom”. This inspired the techniques to improve the single molecule measurements. Since the first single molecule study was in 1961, it has been developed in various field and evolved into powerful tools to understand chemical and biological property of molecules. This thesis demonstrates electronic single molecule measurement with Scanning Tunneling Microscopy (STM) and two of applications of STM; Break Junction (BJ) and Recognition Tunneling (RT). First, the two series of carotenoid molecules with four different substituents were investigated to show how substituents relate to the conductance and molecular structure. The measured …

Contributors
Im, JongOne, Lindsay, Stuart M, Zhang, Peiming, et al.
Created Date
2016

This dissertation features a compilation of studies concerning the biophysics of multicellular systems. I explore eukaryotic systems across length scales of the cell cytoskeleton to macroscopic scales of tissues. I begin with a general overview of the natural phenomena of life and a philosophy of investigating developmental systems in biology. The topics covered throughout this dissertation require a background in eukaryotic cell physiology, viscoelasticity, and processes of embryonic tissue morphogenesis. Following a brief background on these topics, I present an overview of the Subcellular Element Model (ScEM). This is a modeling framework which allows one to compute the dynamics of …

Contributors
Sandersius, Sebastian Ambrose, Newman, Timothy J, Rez, Peter, et al.
Created Date
2011

Breast cancer cell invasion is a highly orchestrated process driven by a myriad of complex microenvironmental stimuli. These complexities make it difficult to isolate and assess the effects of specific parameters including matrix stiffness and tumor architecture on disease progression. In this regard, morphologically accurate tumor models are becoming instrumental to perform fundamental studies on cancer cell invasion within well-controlled conditions. In this study, the use of photocrosslinkable hydrogels and a novel, two-step photolithography technique was explored to microengineer a 3D breast tumor model. The microfabrication process presented herein enabled precise localization of the cells and creation of high stiffness …

Contributors
Sam, Feba, Nikkhah, Mehdi, Ros, Robert, et al.
Created Date
2015

Bio-molecules and proteins are building blocks of life as is known, and understanding their dynamics and functions are necessary to better understand life and improve its quality. While ergodicity and fluctuation dissipation theorem (FDT) are fundamental and crucial concepts regarding study of dynamics of systems in equilibrium, biological function is not possible in equilibrium. In this work, dynamical and orientational structural crossovers in low-temperature glycerol are investigated. A sudden and notable increase in the orientational Kirk- wood factor and the dielectric constant is observed, which appears in the same range of temperatures that dynamic crossover of translational and rotational dynamics …

Contributors
Seyedi, seyed salman, Matyushov, Dmitry V, Beckstein, Oliver, et al.
Created Date
2018

A distinct characteristic of ferroelectric materials is the existence of a reversible spontaneous polarization with the application of an electric field. The relevant properties ferroelectric lithium niobate surfaces include a low density of defects and external screening of the bound polarization charge. These properties result in unique surface electric field distribution with a strong electric field in the vicinity of domain boundaries, while away from the boundaries, the field decreases rapidly. In this work, ferroelectric lithium niobate (LN) is used as a template to direct the assembly of metallic nanostructures via photo-induced reduction and a substrate for deposition of ZnO …

Contributors
Sun, Yang, Nemanich, Robert, Bennett, Peter, et al.
Created Date
2011

This work demonstrated a novel microfluidic device based on direct current (DC) insulator based dielectrophoresis (iDEP) for trapping individual mammalian cells in a microfluidic device. The novel device is also applicable for selective trapping of weakly metastatic mammalian breast cancer cells (MCF-7) from mixtures with mammalian Peripheral Blood Mononuclear Cells (PBMC) and highly metastatic mammalian breast cancer cells, MDA-MB-231. The advantage of this approach is the ease of integration of iDEP structures in microfliudic channels using soft lithography, the use of DC electric fields, the addressability of the single cell traps for downstream analysis and the straightforward multiplexing for single …

Contributors
Bhattacharya, Sanchari, Ros, Alexandra, Ros, Alexandra, et al.
Created Date
2013

Human islet amyloid polypeptide (hIAPP), also known as amylin, is a 37-residue intrinsically disordered hormone involved in glucose regulation and gastric emptying. The aggregation of hIAPP into amyloid fibrils is believed to play a causal role in type 2 diabetes. To date, not much is known about the monomeric state of hIAPP or how it undergoes an irreversible transformation from disordered peptide to insoluble aggregate. IAPP contains a highly conserved disulfide bond that restricts hIAPP(1-8) into a short ring-like structure: N_loop. Removal or chemical reduction of N_loop not only prevents cell response upon binding to the CGRP receptor, but also …

Contributors
Cope, Stephanie M., Vaiana, Sara M, Ghirlanda, Giovanna, et al.
Created Date
2013

In disordered soft matter system, amorphous and crystalline components might be coexisted. The interaction between the two distinct structures and the correlation within the crystalline components are crucial to the macroscopic property of the such material. The spider dragline silk biopolymer, is one of such soft matter material that exhibits exceptional mechanical strength though its mass density is considerably small compare to structural metal. Through wide-angle X-ray scattering (WAXS), the research community learned that the silk fiber is mainly composed of amorphous backbone and $\beta$-sheet nano-crystals. However, the morphology of the crystalline system within the fiber is still not clear. …

Contributors
Mou, Qiushi, Yarger, Jeffery, Benmore, Chris, et al.
Created Date
2015

Biophysical techniques have been increasingly applied toward answering biological questions with more precision. Here, three different biological systems were studied with the goal of understanding their dynamic differences, either conformational dynamics within the system or oligomerization dynamics between monomers. With Cy3 on the 5' end of DNA, the effects of changing the terminal base pair were explored using temperature-dependent quantum yields. It was discovered, in combination with simulations, that a terminal thymine base has the weakest stacking interactions with the Cy3 dye compared to the other three bases. With ME1 heterodimers, the goal was to see if engineering a salt …

Contributors
Binder, Jennifer K., Levitus, Marcia, Wachter, Rebekka, et al.
Created Date
2015

Mechanical properties (e.g. deformability or stiffness) are critical to a cancer cell's ability to maneuver through and exert forces upon the extracellular matrix, and thus affect its ability to metastasize. §3.1 introduces the experimental method combining atomic force microscope (AFM) based indentation and confocal laser scanning microscopy (CLSM). §3.2 presents a method combining AFM and confocal microscopy (AFM stiffness nanotomography), and results on normal and pre-cancerous esophageal cells which indicate that even in the earliest stages, cancer cells exhibit increased deformability. §3.3 presents experimental results on weakly metastatic breast cancer cells that compare well with values obtained from other experimental …

Contributors
Staunton, Jack Rory, Ros, Robert, Lindsay, Stuart M., et al.
Created Date
2014

Driven by the curiosity for the secret of life, the effort on sequencing of DNAs and other large biopolymers has never been respited. Advanced from recent sequencing techniques, nanotube and nanopore based sequencing has been attracting much attention. This thesis focuses on the study of first and crucial compartment of the third generation sequencing technique, the capture and translocation of biopolymers, and discuss the advantages and obstacles of two different nanofluidic pathways, nanotubes and nanopores for single molecule capturing and translocation. Carbon nanotubes with its constrained structure, the frictionless inner wall and strong electroosmotic flow, are promising materials for linearly …

Contributors
Song, Weisi, Lindsay, Stuart, Ros, Robert, et al.
Created Date
2015

One dimensional (1D) and quasi-one dimensional quantum wires have been a subject of both theoretical and experimental interest since 1990s and before. Phenomena such as the "0.7 structure" in the conductance leave many open questions. In this dissertation, I study the properties and the internal electron states of semiconductor quantum wires with the path integral Monte Carlo (PIMC) method. PIMC is a tool for simulating many-body quantum systems at &#64257;nite temperature. Its ability to calculate thermodynamic properties and various correlation functions makes it an ideal tool in bridging experiments with theories. A general study of the features interpreted by the …

Contributors
Liu, Jianheng, Shumway, John B, Schmidt, Kevin E, et al.
Created Date
2012

This dissertation presents research findings regarding the exploitation of localized surface plasmon (LSP) of epitaxial Ag islands as a means to enhance the photoluminescence (PL) of Germanium (Ge) quantum dots (QDs). The first step of this project was to investigate the growth of Ag islands on Si(100). Two distinct families of Ag islands have been observed. “Big islands” are clearly faceted and have basal dimensions in the few hundred nm to μm range with a variety of basal shapes. “Small islands” are not clearly faceted and have basal diameters in the 10s of nm range. Big islands form via a …

Contributors
Kong, Dexin, Drucker, Jeffery, Chen, Tingyong, et al.
Created Date
2015

Fluorescence spectroscopy is a popular technique that has been particularly useful in probing biological systems, especially with the invention of single molecule fluorescence. For example, Förster resonance energy transfer (FRET) is one tool that has been helpful in probing distances and conformational changes in biomolecules. In this work, important properties necessary in the quantification of FRET were investigated while FRET was also applied to gain insight into the dynamics of biological molecules. In particular, dynamics of damaged DNA was investigated. While damages in DNA are known to affect DNA structure, what remains unclear is how the presence of a lesion, …

Contributors
Stennett, Elana Maria Shepherd, Levitus, Marcia, Ros, Robert, et al.
Created Date
2015

Proteins are essential for most biological processes that constitute life. The function of a protein is encoded within its 3D folded structure, which is determined by its sequence of amino acids. A variation of a single nucleotide in the DNA during transcription (nSNV) can alter the amino acid sequence (i.e., a mutation in the protein sequence), which can adversely impact protein function and sometimes cause disease. These mutations are the most prevalent form of variations in humans, and each individual genome harbors tens of thousands of nSNVs that can be benign (neutral) or lead to disease. The primary way to …

Contributors
Butler, Brandon Mac, Ozkan, S. Banu, Vaiana, Sara, et al.
Created Date
2016

The atomic force microscope (AFM) is capable of directly probing the mechanics of samples with length scales from single molecules to tissues and force scales from pico to micronewtons. In particular, AFM is widely used as a tool to measure the elastic modulus of soft biological samples by collecting force-indentation relationships and fitting these to classic elastic contact models. However, the analysis of raw force-indentation data may be complicated by mechanical heterogeneity present in biological systems. An analytical model of an elastic indentation on a bonded two-layer sample was solved. This may be used to account for substrate effects and …

Contributors
Doss, Bryant Lee, Ros, Robert, Lindsay, Stuart, et al.
Created Date
2015

This thesis describes several approaches to next generation DNA sequencing via tunneling current method based on a Scanning Tunneling Microscope system. In chapters 5 and 6, preliminary results have shown that DNA bases could be identified by their characteristic tunneling signals. Measurements taken in aqueous buffered solution showed that single base resolution could be achieved with economic setups. In chapter 7, it is illustrated that some ongoing measurements are indicating the sequence readout by making linear scan on a piece of short DNA oligomer. However, to overcome the difficulties of controlling DNA especially ssDNA movement, it is much better to …

Contributors
Huang, Shuo, Lindsay, Stuart, Sankey, Otto, et al.
Created Date
2011

One of the most important issues in femtosecond free electron laser X-ray diraction is to reconstruct the 3D charge density of molecule from a mass of diraction snapshots. In order to determine the orientation of single molecule from diraction patterns, we rst determine the moments and products of inertia of this from 2D experiment data (diraction patterns or EM images to obtain the elements of the inertia tensor. If diraction patterns from uniformly random orientations or some preferred orientations are collected, the principal axes of the molecule can be extracted, together with the Euler angles which relate the principal axes …

Contributors
Wang, Xiaoyu, Spence, John C.H., Schmidt, Kevin, et al.
Created Date
2011

Cell adhesion is an important aspect of many biological processes. The atomic force microscope (AFM) has made it possible to quantify the forces involved in cellular adhesion using a technique called single cell force spectroscopy (SCFS). AFM based SCFS offers versatile control over experimental conditions for probing directly the interaction between specific cell types and specific proteins, surfaces, or other cells. Transmembrane integrins are the primary proteins involved in cellular adhesion to the extra cellular matix (ECM). One of the chief integrins involved in the adhesion of leukocyte cells is αMβ2 (Mac-1). The experiments in this dissertation quantify the adhesion …

Contributors
Christenson, Wayne B, Ros, Robert, Beckstein, Oliver, et al.
Created Date
2016

Na+/H+ antiporters are vital membrane proteins for cell homeostasis, transporting Na+ ions in exchange for H+ across the lipid bilayer. In humans, dysfunction of these transporters are implicated in hypertension, heart failure, epilepsy, and autism, making them well-established drug targets. Although experimental structures for bacterial homologs of the human Na+/H+ have been obtained, the detailed mechanism for ion transport is still not well-understood. The most well-studied of these transporters, Escherichia coli NhaA, known to transport 2 H+ for every Na+ extruded, was recently shown to bind H+ and Na+ at the same binding site, for which the two ion species …

Contributors
Dotson, David Lee, Beckstein, Oliver, Ozkan, Sefika B, et al.
Created Date
2016

Proteins are a fundamental unit in biology. Although proteins have been extensively studied, there is still much to investigate. The mechanism by which proteins fold into their native state, how evolution shapes structural dynamics, and the dynamic mechanisms of many diseases are not well understood. In this thesis, protein folding is explored using a multi-scale modeling method including (i) geometric constraint based simulations that efficiently search for native like topologies and (ii) reservoir replica exchange molecular dynamics, which identify the low free energy structures and refines these structures toward the native conformation. A test set of eight proteins and three …

Contributors
Glembo, Tyler, Ozkan, Sefika B, Thorpe, Michael F, et al.
Created Date
2011

Photosystem II (PSII) is a large protein-cofactor complex. The first step in photosynthesis involves the harvesting of light energy from the sun by the antenna (made of pigments) of the PSII trans-membrane complex. The harvested excitation energy is transferred from the antenna complex to the reaction center of the PSII, which leads to a light-driven charge separation event, from water to plastoquinone. This phenomenal process has been producing the oxygen that maintains the oxygenic environment of our planet for the past 2.5 billion years. The oxygen molecule formation involves the light-driven extraction of 4 electrons and protons from two water …

Contributors
Basu, Shibom, Fromme, Petra, Spence, John C.H., et al.
Created Date
2015

In this work, atomic force microscopy (AFM) and time resolved confocal fluorescence microscopy are combined to create a microscopy technique which allows for nanometer resolution topographic and fluorescence imaging. This technique can be applied to any sample which can be immobilized on a surface and which can be observed by fluorescence microscopy. Biological problems include small molecular systems, such as membrane receptor clusters, where very high optical resolutions need to be achieved. In materials science, fluorescent nanoparticles or other optically active nanostructures can be investigated using this technique. In the past decades, multiple techniques have been developed that yield high …

Contributors
Schulz, Olaf, Ros, Robert, Levitus, Marcia, et al.
Created Date
2012

My research centers on the design and fabrication of biomolecule-sensing devices that combine top-down and bottom-up fabrication processes and leverage the unique advantages of each approach. This allows for the scalable creation of devices with critical dimensions and surface properties that are tailored to target molecules at the nanoscale. My first project focuses on a new strategy for preparing solid-state nanopore sensors for DNA sequencing. Challenges for existing nanopore approaches include specificity of detection, controllability of translocation, and scalability of fabrication. In a new solid-state pore architecture, top-down fabrication of an initial electrode gap embedded in a sealed nanochannel is …

Contributors
Sadar, Joshua Stephen, Qing, Quan, Lindsay, Stuart, et al.
Created Date
2019