Molecular, Cellular, and Tissue Engineering Commons^™

Targeting Myeloid Cell Iron Metabolism In Salmonella-Induced Colitis, Mariella Arcos Padilla

Biomedical Engineering ETDs

Salmonellosis is a severe infection caused by Salmonella enterica serovar Typhimurium, leading to significant global morbidity and mortality.

Previous studies have shown that mice lacking the iron storage protein ferritin heavy chain (FTH1) in myeloid cells exhibit worsened Salmonella infection. Nuclear receptor co-activator 4 (NCOA4) directs FTH1 autophagic degradation to release iron from storage during conditions of low iron. However, the role of myeloid NCOA4 in regulating bacterial infections remains unclear.

Here, we found that myeloid NCOA4 deficiency augments spleen iron levels and increases cellular iron accumulation, oxidative stress, and ferroptosis in bone marrow-derived macrophages (BMDM) cells. This deficiency also …

Engineered Nucleic-Acid Binding Intrinsically Disordered Proteins For Biomedical Applications, Telmo Diez Perez

Biomedical Engineering ETDs

This dissertation explores the use of intrinsically disorder proteins (IDPs) in biomedical applications related to the detection and biosensing of nucleic-acid species. We engineer several low critical solution temperature (LCST) nucleic-acid binding elastin-like polypeptides (ELPs) as model IDPs and study their potential in biomedical application via interactions with short single-stranded (ss) DNA, tRNA and viral RNAs. First, we engineer a simple polycationic ELP capable of recruiting DNA on demand in a DNA-protein-rich condensate via LLPS. Moreover, we develop a modified Flory-Huggins theory to quantify the partitioning of DNA and protein upon coacervate formation with and without salts. We then design …

Fumarate-Based Polymers: Oligo(Poly(Ethylene Glycol) Fumarate) And Poly(Butylene Fumarate) For Tissue Engineering Heart Valve And Bone Tissue, Christian T. Denny

Biomedical Engineering ETDs

Tissue engineering is an emerging field that came from the fields of medicine, materials science, and engineering. The foundation of tissue engineering uses a paradigm that incorporates cells, biomaterials, and exogenous factors to create living tissues for medical, pharmaceutical, and research purposes. Within the last 100 years, biomaterials have been developed to solve many medical and research problems. As biomaterials have developed throughout the years new materials have been developed to have specific properties appropriate for medical applications. Fumarate is a naturally derived molecule in the body and has been found useful for developing polyesters that can be crosslinked into …

Characterization Of Phase Behavior In Idp Solutions By Uv-Vis Spectrophotometry And Phase Volume Fraction Measurements In Capillaries, Qing Sun

Biomedical Engineering ETDs

Intrinsically disordered proteins (IDPs) play vital roles in cell signaling and regulation by changing conformation dynamically under various stimulus. Thus, it is crucial to understand their physical properties in vitro especially liquid-liquid phase separation (LLPS). Here, we first used UV-vis spectrophotometry to investigate two of IDPs' physical properties – transition temperature (Tt) and coacervate size. This deeper insight allows us to further understand the dynamics of phase growth. We then constructed a binodal curve in the phase diagram by measurement of volume ratios in phase separated IDP solution in glass capillaries.

Correlating Diffusional Dynamics And Receptor Tyrosine Kinase Function Using Single Quantum Dot Tracking, Irais Ortiz Caraveo

Biomedical Engineering ETDs

Epidermal growth factor receptor (EGFR) signal transduction is initiated via ligand (EGF) binding, followed by dimerization, autophosphorylation of the C-terminal tails, and recruitment of proteins that form a larger signaling complex to propagate the signal. We explored the relationship between receptor mobility and signaling using single-particle tracking (SPT) by examining the diffusional dynamics of EGFR and two truncation mutants to understand whether mobility changes are correlated with signaling. Results revealed that phosphorylation of the C-terminal tail of EGFR is required for maximal reduction in mobility that occurs with EGF stimulation, indicating that receptor mobility is a read-out for receptor signaling. …

Photo-Characterization Of Selective Luminescent Protein Aggregate Sensors - Oligo-P-Phenylene Ethynylene (Opes), Florencia A. Monge

Biomedical Engineering ETDs

Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease,

and related tauopathies, are a global health care challenge due to the lack of early

treatment and diagnostic options. These diseases take an emotional and physical

toll on patients, caretakers, and a rather large economic toll on taxpayer-based

health care systems. The pathologies of these diseases are characterized by the

aggregation of misfolded proteins, amyloid-β (Aβ) and tau, into β-sheet rich

structures called amyloids. Research has found that the presence of protein

aggregates predates cognitive symptoms by years. Current diagnostic tools are

based on the detection of these amyloid aggregates, historically by …

Developing A Synthetic Model Of The Candida Albicans Cell Wall Using Self-Assembled Monolayers To Host Beta-Glucan As Ligands, Ushnik Ghosh

Biomedical Engineering ETDs

The goal of this investigation is to study mechanisms the immune cell receptor, Dectin-1, uses to identify the fungal cell species, Candida albicans. Dectin-1 identifies extracellular matrix polysaccharides that Candida albicans express known as β-glucan. To study the interaction of β-glucan – Dectin-1 at the nanoscopic scale, the investigators of this project have endeavored to model the Candida albicans cell wall with engineered Self-Assembled Monolayers presenting β-glucan as a ligand for immobilized Dectin-1 receptors. By engineering a simplified ex-vivo model of the Candida albicans cell wall, the investigators of this study aim to gain precise control of the composition …

Incorporation Of Egfr And Ron Receptors Into Nanodiscs, Cristina Flores-Cadengo

Biomedical Engineering ETDs

Understanding the structure-function relationship of membrane receptors is essential to comprehend the crosstalk between key signaling pathways. Aberrant trans-activation between receptors can lead to tumorigenesis. Two of these receptors known to be involved in cancer development are receptor tyrosine kinases (RTKs), RON (Recepteur d'Origine Nantais) and EGFR (Epidermal Growth Factor Receptor). There has been evidence of heterodimerization and crosstalk between these two receptors based on co-immunoprecipitation, however the structural requirements behind these interactions remain unknown. Structural studies could provide insights into these RTKs’ modes of dimerization and structure-function relationship. However, structural studies of full-length membrane proteins are often difficult due …