Biomedical Engineering and Bioengineering Commons^™

Rational Design Of Peptide-Based Materials Informed By Multiscale Molecular Dynamics Simulations, Dhwanit Rahul Dave

Dissertations, Theses, and Capstone Projects

The challenge of establishing a sustainable and circular economy for materials in medicine and technology necessitates bioinspired design. Nature's intricate machinery, forged through evolution, relies on a finite set of biomolecular building blocks with through-bond and through-space interactions. Repurposing these molecular building blocks requires a seamless integration of computational modeling, design, and experimental validation. The tools and concepts developed in this thesis pioneer new directions in peptide-materials design, grounded in fundamental principles of physical chemistry. We present a synergistic approach that integrates experimental designs and computational methods, specifically molecular dynamics simulations, to gain in-depth molecular insights crucial for advancing the …

Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov

Doctoral Dissertations

Reactive chemistries for protein chemical modification play an instrumental role in chemical biology, proteomics, and therapeutics. Depending on the application, the selectivity of these modifications can range from precise modification of an amino acid sequence by genetic manipulation of protein expression machinery to a stochastic modification of lysine residues on the protein surface. Ligand-Directed (LD) chemistry is one of the few methods for targeted modification of endogenous proteins without genetic engineering. However, current LD strategies are limited by stringent amino acid selectivity. To bridge this gap, this thesis focuses on the development of highly reactive LD Triggerable Michael Acceptors (LD-TMAcs) …

Evolutionary Conservation And Times Of Action Of Heterochronic Genes, Maria Ivanova

Theses and Dissertations

The heterochronic pathway of C. elegans is the most well-characterized system to date for controlling the sequence and timing of developmental events. However, we still have critical unanswered questions to address. First, little is known about the evolution of the heterochronic pathway, and of developmental timing in general. To determine if the roles of major heterochronic genes are conserved, I made mutants in orthologs of these genes in C. briggsae, using CRISPR/Cas9. My studies revealed a significant drift in the roles of some of the genes, although all of them are still involved in the developmental timing regulation, and several …

Construction And Performance Optimization Of Bioconjugated Nanosensors For Early Detection Of Breast Cancer And Pro-Inflammatory Diseases, Pooja Gaikwad

Dissertations, Theses, and Capstone Projects

In recent years, nanosensors have emerged as a tool with strong potential in medical diagnostics. Single-walled carbon nanotube (SWCNT) based optical nanosensors have notably garnered interest due to the unique characteristics of their near-infrared fluorescence emission, including tissue transparency, photostability, and various chiralities with discrete absorption and fluorescence emission bands. Additionally, the optoelectronic properties of SWCNT are sensitive to the surrounding environment, which makes them suitable for in vitro and in vivo biosensing. Single-stranded (ss) DNA-wrapped SWCNTs have been reported as optical nanosensors for cancers and metabolic diseases. Breast cancer and cardiovascular diseases are the most common causes of death …

Towards Clinical Microscopic Fractional Anisotropy Imaging, Nico Jj Arezza

Electronic Thesis and Dissertation Repository

Microscopic fractional anisotropy (µFA) is a diffusion-weighted magnetic resonance imaging (dMRI) metric that is sensitive to neuron microstructural features without being confounded by the orientation dispersion of axons and dendrites. µFA may potentially act as a surrogate biomarker for neurodegeneration, demyelination, and other pathological changes to neuron microstructure with greater specificity than other dMRI techniques that are sensitive to orientation dispersion, such as diffusion tensor imaging. As with many advanced imaging techniques, µFA is primarily used in research studies and has not seen use in clinical settings.

The primary goal of this Thesis was to assess the clinical viability of …

Antimicrobial Activity And Mechanism Of Amyloid Proteins And Synthetic Conjugated Polyelectrolytes, Fahimeh Maghsoodi

Nanoscience and Microsystems ETDs

Although the exact cause of Alzheimer’s disease (AD) is still unknown, it is widely considered that the accumulation of amyloid plaques composed of the amyloid-β (Aβ) peptide in the brain is linked to neurodegeneration. Co-localization of viral DNA with Aβ plaques, the association of brain infection and AD, and research indicating the protective effect of Aβ against bacteria and fungi in mice and human cells have led to the hypothesis that Aβ expression and deposition may be central to its function as an antimicrobial peptide (AMP). In my thesis research, we seek to elucidate how Aβ functions as an AMP …

Nanosecond Pulsed Electric Field Modulates Electron Transport And Mitochondrial Structure And Function, Lucas Nelson Potter

Biomedical Engineering Theses & Dissertations

Pulsed power treatment has been used to induce regulated cell death (RCD) in cells or ablate tumors in animals. A subset of pulsed power as electroporation with high voltage and pulse duration of milliseconds is used for biomedical treatment to induce pores in the plasma membrane of cells. Nanosecond Pulsed Electric Fields (nsPEFs)– an extension of electroporation, uses waveforms with pulse durations on the order of 10-900 nanoseconds. nsPEF treatment has demonstrated intracellular effects for potential biomedical applications. In this work, nsPEF treatment is used to demonstrate changes that affect viability, plasma membrane permeability ROS (Reactive Oxygen Species) in the …

Angiogenic Supports For Microvascular Engineering, Zain Siddiqui

Dissertations

Ischemic tissue disease is caused by a lack of circulation / blood supply to tissue. This can be treated by introducing a number of angiogenic (pro-blood vessel forming) factors into the tissue. This work presents strategies for ischemic tissue treatment utilizing a novel proangiogenic self-assembling peptide hydrogel platform. To demonstrate the utility of this platform, its use alone as an angiogenic therapeutic (both alone as a self-assembling hydrogel and with two-component systems), and its ability to vascularize implants is explored. Due to these angiogenic scaffolds demonstrating efficacy to regenerate microvasculature, this work evaluates diseases that can be treated by the …

Encapsulation Of Antimicrobial Peptides In Bicontinuous Microemulsions For Topical Delivery To Surgical Site Infections And Chronic Wounds, Madison A. Oehler

Masters Theses

Surgical site infections and chronic wounds, especially those caused by antibiotic-resistant microorganisms, result in hospitalization and fatalities each year. Methods to prevent these infections, such as cleaning and preparing medical tools, have had minimal success in preventing infections. Further, antibiotic treatments have become less successful in treating infections and wounds because of antibiotic-resistant bacteria. Antimicrobial peptides (AMP) are a possible treatment solution for wound infections. AMPs are oligopeptides that occur in nature or can be synthesized in vitro which possess a broad spectrum of antimicrobial activity against bacteria and other harmful microorganisms. AMPs operate by disrupting the packing arrangements of …

Re-Engineering Cardio-Oncology Testing Using Biomimetic Heart Slice Cultures., Jessica Miller

Electronic Theses and Dissertations

28% of drug withdrawal from the market are due to unforeseen disruptions in cardiomyocyte contractility and electrophysiology. The most commonly used platforms for drug testing are in vivo animal models and in vitro cell culture models. While both have been of paramount importance for the discovery and detection of many cardiotoxicities and mechanisms of action, they lack the ability to model an intact human myocardium. This work aims to establish cardiac tissue slices, which are 300-micron thin tissue sections taken from the left ventricular myocardium, as an alternative platform for cardio-oncology studies, specifically cardiotoxicity testing. Additionally, this work aims to …

Role Of Ligand Architecture On Collective Cell Invasion, Amrit Bagchi

McKelvey School of Engineering Theses & Dissertations

Epithelial cell collectives utilize extra-cellular matrix (ECM) fibers to undergo collective migration critical in regeneration, repair and cancer metastasis. However, very little is known about the various factors which determine the ability of cellular collectives to utilize ECM fibers to undergo these critical processes in-vivo. First part of the dissertation focusses on understanding how cell collectives exploit specific properties, like stiffness and fiber length to undergo collective streaming. It is also unclear how cellular forces, cell-cell adhesion, and velocities are coordinated within streams. To independently tune stiffness and collagen fiber length, we developed new hydrogels and discovered invasion-like streaming of …

Ligand- And Strain-Specific Control Of Microbial Communities, Austin Grant Rottinghaus

McKelvey School of Engineering Theses & Dissertations

Microbes naturally coexist in complex, multi-strain communities that are valuable assets for their host. Commensal and probiotic microbes prevent pathogen colonization, reduce the frequency and severity of various ailments, provide essential nutrients, and offer various additional benefits. Understanding the dynamics of and tailoring microbial communities to provide additional beneficial functions is a primary focus of researchers in medicine and agriculture. To date, consortia have primarily been manipulated by supplementing the communities with microbes that were engineered in vitro or by introducing stimuli that alter the metabolism or composition of the community. This method has proven successful, with numerous microbes engineered …

A Protein-Based Therapeutic Combination For The Treatment Of Hard-To-Heal Wounds, Graham L. Strauss

USF Tampa Graduate Theses and Dissertations

Chronic wounds present many clinical challenges in relation to the successful treatment and closure of the damaged tissue. Most current treatment methods focused on one or two aspects to drive wound closure, while most chronic wounds are multifactorial environments with many of those dependencies relying on the termination of one another to effectively gain tissue construction, closure, and full skin thickness and composition. Natural wound healing processes allude to potential biologics that can impede the chronic breakdown of tissue, while restoring deposition of new tissue, and effectively leading to a healed wound. Proteases secreted by the body’s immune system lay …

Characterizing Mechanical Regulation Of Bone Metastatic Breast Cancer Cells, Boyuan Liu

Doctoral Dissertations

Breast cancer most frequently metastasizes to the skeleton. Bone metastatic cancer is incurable and induces wide-spread bone osteolysis, resulting in significant patient morbidity and mortality. Mechanical stimuli in the skeleton are an important microenvironmental parameter that modulates tumor formation, osteolysis, and tumor cell-bone cell signaling, but which mechanical signals are the most beneficial and the corresponding molecular mechanisms are unknown. This work focused on bone matrix deformation and interstitial fluid flow based on their well-known roles in bone remodeling and in primary breast cancer. The goal of our research was to establish a platform that could define the relationship between …

Characterization Of A Malachite Green Dna Aptamer And Development Of Malachite Green Dna Aptamer Sensor, Martin O'Steen

Electronic Theses and Dissertations, 2020-

Hydrogels have been extensively studied for use in applications such as tissue engineering, drug delivery systems, wound dressing, actuators, valves, and sensors in Micromechanical Systems (MEMS), among others. Thermo-responsive hydrogels in particular pose various advantages such as their capability to respond to an external stimulus and reverse the response when the stimulus is removed and the ability to imbibe a significant amount of solvent and increase their volume by over 1000%. Extensive research has been conducted to tune and improve hydrogel's rate and degree of swelling and mechanical properties. Previous work showed that when synthetic clay (Laponite) is cross-linked with …

Challenges Of Constructing Entrainment Map For Arbitrary Circadian Models, Yuxuan (Nelson) Wu

Honors Theses

The entrainment map, developed by Dr.Diekman and Dr.Bose, is claimed to be a 1-dimensional map that produces a better prediction for phase-locking than methods than the phase response curve for circadian models. In his paper, he constructs the entrainment map for the two-dimensional circadian model, the Novak-Tyson model, and the other two higher-dimensional circadian models. For this thesis, we concentrate on exploring if it is viable to construct the entrainment map for other circadian models that are not included in his paper: the Becker-Weimann model and the Relogio model. In addition, we discuss the challenges of constructing the entrainment map …

Investigating Effects Of Microenvironmental Stress On Cell Metabolism Using Multiphoton Imaging, Lisa Rebello

Graduate Theses and Dissertations

Resistance to therapy in cancer is a major cause of poor prognosis in patients. Tumor hypoxia plays an active role in mediating treatment resistance and has been linked to metastases and metastatic potential in cancer. Our research focused on three objectives: i) To understand metabolic effects of chronic and intermittent hypoxia in murine breast cancer cells and its affiliation with metastatic potential ii) To identify the metabolic changes associated with radiation therapy in a panel of radiosensitive and radioresistant human head and neck cancer cells and iii) to monitor the changes in cell metabolism associated with gain of treatment resistance. …

Role Of The Nuclear Envelope In The Mechanoregulation Adipogenesis, Matthew H. Goelzer

Boise State University Theses and Dissertations

Mechanical signals are known regulators of mesenchymal stem cell (MSC) fate, regulating their differentiation into osteoblasts, chondrocytes, and adipocytes. These relevant mechanical signals reach to nucleus through nuclear envelope proteins such as Lamin A/C and the Linker of the Nucleoskeleton and Cytoskeleton (LINC) complexes. Within the context of bone, clinically relevant mutations of Lamin A/C and the LINC complexes have been shown to alter adipogenic and osteogenic MSC differentiation patterns, suggesting that that nucleo-cytoskeletal connectivity provided by nuclear envelope is important in regulating MSC fate. Using MSC adipogenesis as a model of MSC mechanical regulation, the goal of this work …

Tools And Strategies For The Patterning Of Bioactive Molecules And Macromolecules, Daniel J. Valles

Dissertations, Theses, and Capstone Projects

Hypersurface Photolithography (HP) is a printing method for fabricating structures and patterns composed of soft materials bound to solid surfaces and with ~1 micrometer resolution in the x, y, and z dimensions. This platform leverages benign, low intensity light to perform photochemical surface reactions with spatial and temporal control of irradiation, and, as a result, is particularly useful for patterning delicate organic and biological material. In particular, surface- initiated controlled radical polymerizations can be leveraged to create arbitrary polymer and block- copolymer brush patterns. Chapter 1 will review the advances in instrumentation architectures from our group that have made these …

Molecular Dynamics Simulations Of Self-Assemblies In Nature And Nanotechnology, Phu Khanh Tang

Dissertations, Theses, and Capstone Projects

Nature usually divides complex systems into smaller building blocks specializing in a few tasks since one entity cannot achieve everything. Therefore, self-assembly is a robust tool exploited by Nature to build hierarchical systems that accomplish unique functions. The cell membrane distinguishes itself as an example of Nature’s self-assembly, defining and protecting the cell. By mimicking Nature’s designs using synthetically designed self-assemblies, researchers with advanced nanotechnological comprehension can manipulate these synthetic self-assemblies to improve many aspects of modern medicine and materials science. Understanding the competing underlying molecular interactions in self-assembly is always of interest to the academic scientific community and industry. …

Evaluation Of Horizontal Gene Transfer Between Genetically Engineered Cyanobacteria And Gram-Negative Bacteria, Andriana Chrysovalanti Zourou

Chemistry & Biochemistry Theses & Dissertations

As the world population is increasing and societies become more technology driven, there is an imperative to develop ‘green energy’ sources to protect our planet. Cyanobacteria that have been genetically engineered to produce organic compounds that may be burnt as fuels show great potential, as they are an environmentally friendly and self-renewable, net carbon-neutral option. However, there are potential risks in the development and use of genetically modified organisms (GMOs). We need to understand in advance the risks that GMOs may pose to our environment and to animal and human health. This will enable experimental procedures, containment strategies and policies …

Electrohydrodynamic Simulations Of Capsule Deformation Using A Dual Time-Stepping Lattice Boltzmann Scheme, Charles Leland Armstrong

Mathematics & Statistics Theses & Dissertations

Capsules are fluid-filled, elastic membranes that serve as a useful model for synthetic and biological membranes. One prominent application of capsules is their use in modeling the response of red blood cells to external forces. These models can be used to study the cell’s material properties and can also assist in the development of diagnostic equipment. In this work we develop a three dimensional model for numerical simulations of red blood cells under the combined influence of hydrodynamic and electrical forces. The red blood cell is modeled as a biconcave-shaped capsule suspended in an ambient fluid domain. Cell deformation occurs …

Computational Algorithms For Predicting Membrane Protein Assembly From Angstrom To Micron Scale, Nandhini Rajagopal

Dissertations - ALL

Biological barriers in the human body are one of the most crucial interfaces perfected through evolution for diverse and unique functions. Of the wide range of barriers, the paracellular protein interfaces of epithelial and endothelial cells called tight junctions with high molecular specificities are vital for homeostasis and to maintain proper health. While the breakdown of these barriers is associated with serious pathological consequences, their intact presence also poses a challenge to effective delivery of therapeutic drugs. Complimenting a rigorous combination of in vitro and in vivo approaches to establishing the fundamental biological construct, in addition to elucidating pathological implications …

Computational Algorithms For Predicting Membrane Protein Assembly From Angstrom To Micron Scale, Nandhini Rajagopal

Dissertations - ALL

Biological barriers in the human body are one of the most crucial interfaces perfected through evolution for diverse and unique functions. Of the wide range of barriers, the paracellular protein interfaces of epithelial and endothelial cells called tight junctions with high molecular specificities are vital for homeostasis and to maintain proper health. While the breakdown of these barriers is associated with serious pathological consequences, their intact presence also poses a challenge to effective delivery of therapeutic drugs. Complimenting a rigorous combination of in vitro and in vivo approaches to establishing the fundamental biological construct, in addition to elucidating pathological implications …

Analyzing The Effects Of E-Hook Peptides On Kinesin-1, Ashton Ward Murrah, Baylee Hope Howard

Honors Theses

Cancer is the second leading cause of death in the United States. Cancerous growth is a result of oncogenes, or mutated genes that increase the rate of cell division in an uncontrolled manner. Cell division, which consists of mitosis and cytokinesis phases, is dependent upon the active movement of kinesin motor proteins along microtubules to rearrange the cytoskeleton for equitable distribution of genetic material to daughter cells. As kinesins are vital to this process, if we could prevent kinesin from binding to the microtubules, cell division would cease.

The goal of this study is to develop a method to prevent …

Uncovering The Roles And Evolved Sequence Grammar Of Hypervariable Intrinsically Disordered Proteins In Bacterial Cell Division, Megan Cohan

McKelvey School of Engineering Theses & Dissertations

Across all domains of life, a defining hallmark of the onset of cell division is the formation of a cytokinetic ring at the center of the cell. Cell division is a tightly controlled process that involves various regulatory factors that modulate the assembly of the cytokinetic ring. In rod-shaped bacteria, the ring is termed the Z-ring after the protein FtsZ, which is foundational to ring formation and is the bacterial homolog of tubulin. Like tubulin, FtsZ is an assembling GTPase, where GTP binding promotes the cooperative assembly into FtsZ polymers that laterally associate to form bundles. While the GTPase domain …

A Mechanism Behind The Mechanotransduction Of Surface Characteristics In Osteoblasts, Otto J. Juhl Iv

Theses and Dissertations

Biomaterials for use in bone regeneration and healing range from metal and metal alloy implants to hydrogel-based solutions. These materials can be optimized to increase bone healing and integration by improving the mechanical and biological properties. Regardless of the material itself, the cell-substrate interaction is key to the success of the biomaterial once implanted. Substrate surface characteristics such as roughness, wettability, and particle density are well-known contributors to a substrate’s overall osteogenic potential, and therefore the substrate's overall success. Unfortunately, it is still unknown how these substrate surface characteristics are transduced into intracellular signals by cells, preventing specific tailoring of …

Development Of Light Actuated Chemical Delivery Platform On A 2-D Array Of Micropore Structure, Hojjat Rostami Azmand, Hojjat Rostami Azmand

Dissertations and Theses

Localized chemical delivery plays an essential role in the fundamental information transfers within biological systems. Thus, the ability to mimic the natural chemical signal modulation would provide significant contributions to understand the functional signaling pathway of biological cells and develop new prosthetic devices for neurological disorders. In this paper, we demonstrate a light-controlled hydrogel platform that can be used for localized chemical delivery in a high spatial resolution. By utilizing the photothermal behavior of graphene-hydrogel composites confined within micron-sized fluidic channels, patterned light illumination creates the parallel and independent actuation of chemical release in a group of fluidic ports. The …

Controlled Membrane Remodeling By Nanospheres And Nanorods: Experiments Targeting The Design Principles For Membrane-Based Materials, Sarah Zuraw-Weston

Doctoral Dissertations

In this thesis we explore two experimental systems probing the interactions of nanoparticles with lipid bilayer membranes. Inspired by the ability of cell membranes to alter their shape in response to bound particles, we report two experimental studies: one of nanospheres the other of long, slender nano-rods binding to lipid bilayer vesicles and altering the membrane shape. Our work illuminates the role of particle geometry, particle concentration, adhesion strength and membrane tension in how membrane morphology is determined. We combine giant unilamellar vesicles with oppositely charged nanoparticles, carefully tuning adhesion strength, membrane tension and particle concentration. In the case of …

Micro-Physiological Models To Mimic Mucosal Barrier Complexity Of The Human Intestine In Vitro, Abhinav Sharma

Doctoral Dissertations

The mucosal barrier in the intestine is vital to maintain selective absorption of nutrients while protecting internal tissues and maintaining symbiotic relationship with luminal microbiota. This bio-barrier consists of a cellular epithelial barrier and an acellular mucus barrier. Secreted mucus regulates barrier function via in situ biochemical and biophysical interaction with luminal content that continually evolves during digestion and absorption. Increasing evidence suggests that a mucus barrier is indispensable to maintain homeostasis in the gastrointestinal tract. However, the importance of mucus barrier is largely underrated for in vitro mucosal tissue modeling. The major gap is the lack of experimental material …