Biological Engineering Commons^™

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …

Higher Tensile Forces Across Cellular Junctions And An Intact Nuclear Linc Complex Is Required For Epithelial Function And Stability, Fnu Vani Narayanan

Theses and Dissertations

Recent advances in three-dimensional (3D) cell culture systems have provided key insights into the understanding of biochemical and physiological states of native tissue. A significant progress in the field of mechanobiology involves measuring cellular traction forces in a more native 3D environment. However, the effects of mechanical forces exerted across cellular junctions and the nuclear LINC complex, in an organized 3D system has not been investigated thus far. Epithelial cells spontaneously form acini (also known as cysts or spheroids) with a single, fluid-filled central lumen, when grown in 3D matrices. The size of the lumen is dependent on apical secretion …

Extracellular Matrix Nanoparticles Effects On The Lung In Vivo, Brittaney E. Ritchie

Theses and Dissertations

Acute respiratory distress syndrome (ARDS) is a life-threatening condition that causes diffuse alveolar damage and a loss of the extracellular matrix (ECM). This leads to pulmonary edema and lung function deterioration. Our lab has created decellularized porcine lung, electrosprayed ECM nanoparticles that have been previously shown to have pro-regenerative capabilities in vitro.

In this study, the ECM nanoparticle effects on young murine lungs were tested in vivo. An ECM nanoparticle suspension, previously used for the in vitro studies, was aerosolized intratracheally into the lungs using a microsprayer. 24 hours later, the lung mechanics, bronchoalveolar lavage fluid, and histology …

Development Of A Torque-Based Device For The Quantification Of Arm Rigidity In Patients With Parkinson’S Disease, Georgina O. Miller

Theses and Dissertations

Parkinsonian rigidity is caused by the inability of the muscles to relax and extend properly, due to reduced dopamine levels and often begins on one side of the body before spreading contralaterally. The current standard for determining joint rigidity in a clinical setting is a test completed by the clinician based on the feel of the relaxed wrist and elbow joints as they are passively flexed and extended and a series of ordinal rating scales, the Movement Disorder Society’s – Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Hoehn and Yahr Scale (H&Y), and Parkinson’s Disease Questionnaire-39 (PDQ-39). These methods are used …

Immunofluorescence Image Feature Analysis And Clustering Pipeline For Distinguishing Epithelial-Mesenchymal Transition, Shreyas Hirway, Nadiah Hassan, Dr. Christopher Lemmon, Dr. Seth Weinberg

Biology and Medicine Through Mathematics Conference

No abstract provided.

Cell Type And Substrate Dependence Of Fibronectin Properties And Mechanotransduction, Navpreet S. Saini

Theses and Dissertations

Fibronectin is an important protein that is able to bind to other fibronectin molecules and to cell surface receptors. In doing so, the interactions fibronectin can perform is important for the processes of cell migration and tissue formation. Understanding the properties of fibronectin and fibril assembly is useful for areas such as wound healing, where fibronectin molecules are assembled to protect the tissue and to perform other tasks. Because of these reasons, it is important to understand how fibronectin is assembled and how its properties affect the fibril assembly, which in return affects the way the cell matrix operates. Previously …

The Role Of The Mechanical Environment On Cd117+ Endothelial Cell Angiogenesis, Patrick Link

Theses and Dissertations

Angiogenesis is a complex process coordinating cell migration, proliferation, and lumen formation. Changes to the microenvironment regulate angiogenesis through mechanotransduction and cytokine signals. In pulmonary hypertension, something in the process becomes abnormal, resulting in changes to the microenvironment and the formation of a glomerulus of dysfunctional capillaries, called a plexiform lesion. Endothelial cells, expressing CD117 (CD117+ EC clones) increase in the plexiform lesions of pulmonary hypertension, independent of pro-angiogenic VEGF signaling. We hypothesize that the mechanical environment and the macromolecular composition of the extracellular matrix, both, contribute to the aberrant angiogenesis. When we changed the mechanical environment, we changed the …

Exogenous Fniii 12-14 Regulates Tgf-Β1-Induced Markers, Hilmi M. Humeid

Theses and Dissertations

The extracellular matrix protein Fibronectin (FN) plays an important role in cell contractility, differentiation, growth, adhesion, and migration. The 12th -14th Type III repeats of FN (FNIII 12-14), also referred to as the Heparin-II domain, comprise a highly promiscuous growth factor (GF) binding region. This binding domain aids in cellular signaling initiated from the ECM. Additionally, FN has the ability to assemble into fibrils under certain conditions, mostly observed during cell contractile processes such as those that initiate due to upregulation of Transforming Growth Factor Beta 1 (TGF-β1) [1], [2]. Previous work from our lab has shown that self-assembly of …

Development And Validation Of A Novel Resonant Energy Transfer (Fret) Biosensor To Measure Tensile Forces At The Linc Complex In Live Cells, Paul Arsenovic

Theses and Dissertations

There is a large body of evidence supporting the theory that cell physiology largely depends on the mechanical properties of its surroundings or micro-environment. More recently studies have shown that changes to intra-cellular mechanical properties can also have a meaningful impact on cell function and in some cases lead to the progression of ailments or disease. For example, small changes to the protein sequence of a structural nuclear envelope protein called lamin-A is known to cause a variety of neurological and musculoskeletal diseases referred to as laminopathies. Currently, there is little incite into how these mutations lead to disease progression …

The Role Of E-Cadherin Force In The Maintenance Of Homeostasis In Epithelial Acini, Fnu Vani Narayanan

Theses and Dissertations

Numerous three-dimensional model systems have emerged for emulating the biochemical and physiological states of native tissue. Yet little is known about the effects of mechanical forces on cell behavior in the context of an organized tissue structure in three-dimensional cell-culture. Epithelial cells cultured in a three-dimensional environment comprised of extracellular matrix proteins form spheroids of polarized cells. Cellular responses to mechanical cues, generated from dynamic interactions with the extracellular matrix and neighboring cells, are known to influence cellular behavior to a great extent. Previous studies have shown that tumorigenic progression has been frequently linked to the down regulation of E-cadherin, …

Polysaccharide-Based Shear Thinning Hydrogels For Three-Dimensional Cell Culture, Vasudha Surampudi

Theses and Dissertations

The recreation of the complicated tissue microenvironment is essential to reduce the gap between in vitro and in vivo research. Polysaccharide-based hydrogels form excellent scaffolds to allow for three-dimensional cell culture owing to the favorable properties such as capability to absorb large amount of water when immersed in biological fluids, ability to form “smart hydrogels” by being shear-thinning and thixotropic, and eliciting minimum immunological response from the host. In this study, the biodegradable shear-thinning polysaccharide, gellan-gum based hydrogel was investigated for the conditions and concentrations in which it can be applied for the adhesion, propagation and assembly of different mammalian …

Ex Vivo Dna Cloning, Adam B. Fisher

Theses and Dissertations

Genetic engineering of microbes has developed rapidly along with our ability to synthesize DNA de novo. Yet, even with decreasing DNA synthesis costs there remains a need for inexpensive, rapid and reliable methods for assembling synthetic DNA into larger constructs or combinatorial libraries. While technological advances have resulted in powerful techniques for in vitro and in vivo assembly of DNA, each suffers inherent disadvantages. Here, an ex vivo DNA cloning suite using crude cellular lysates derived from E. coli is demonstrated to amplify and assemble DNA containing small sequence homologies. Further, the advantages of an ex vivo approach are …