Browsing by Author "Zignego, Donald Lee"

Now showing 1 - 2 of 2

In vitro and in vivo systems mechanobiology of osteoarthritic chondrocytes
(Montana State University - Bozeman, College of Engineering, 2015) Zignego, Donald Lee; Chairperson, Graduate Committee: Ronald K. June II; Aaron A. Jutila, Martin K. Gelbke and Daniel M. Gannon were co-authors, and Ronald K. June was a corresponding author of the article, 'The mechanical microenviroment of high concentration agarose for applying deformation to primary chondrocytes' in the journal 'Journal of biomechanics' which is contained within this thesis.; Aaron A. Jutila was a main author, Bradley K. Hwang, Jonathan K. Hilmer, Timothy Hamerly, Cody A. Minor and Seth T. Walk were co-authors, and Ronald K. June was a corresponding author of the article, 'Candidate mediators of chondrocyte mechanotransduction via targeted and untargeted metabolomic measurements' in the journal 'Archives of biochemistry and biophysics' which is contained within this thesis.; Carley N. McCutchen, Jonathan K. Hilmer were co-authors, and Ronald K. June was a corresponding author of the article, 'Mechanotransduction in primary human osteoarthritic chondrocytes is mediated by metabolism of energy, lipids, and amino acids' submitted to the journal 'Arthritis and rheumatology' which is contained within this thesis.; Jonathan K. Hilmer was a co-author, and Ronald K. June was a corresponding author of the article, 'Shotgun phosphoproteomics identifies activation of vimentin, ankyrin, vam6/vpS39-like protein in primary human osteoarthritic chondrocytes after mechanical stimulation' submitted to the journal 'eLife' which is contained within this thesis.; Sarah E. Mailhiot, Timothy Hamerly, Edward E. Schmidt were co-authors, and Ronald K. June was a corresponding author of the article, 'Alterations in joint metabolomics following surgical destabilization and exercise in a novel cartilage reporter mouse model' submitted to the journal 'Annals of biomedical engineering' which is contained within this thesis.
All cells are subjected to and respond to mechanical forces, but the underlying processes linking the mechanical stimuli to biological responses are poorly understood. In the joints of the body (e.g. the knee, hip, etc...) articular cartilage serves as a low friction, load bearing material and is subjected to near-constant mechanical loading. Through excessive loading of the joint, usually caused by obesity or injury, the protective articular cartilage begins to diminish, leading to the progression of osteoarthritis (OA). Osteoarthritis is the most common joint disorder in the world and is characterized by the deterioration of articular cartilage. Determining the link between cartilage deterioration and mechanical loading is one motivation that drove this research. Articular cartilage is composed of a dense extracellular matrix (ECM), a less-stiff pericelluar matrix (PCM), and highly specialized cells called chondrocytes. As the sole cell type in cartilage, chondrocytes are responsible for the healthy turnover of the ECM by creating, maintaining, and repairing the matrix. Multiple lines of evidence suggest chondrocytes can transduce mechanical stimuli into biological signals. The hypothesis for this research is that physiologically pertinent loading of chondrocytes results in a specific set of bio-signals resulting in matrix synthesis. To test this hypothesis, two unbiased, large-scale metabolomic and phosphoproteomic datasets were generated by modeling physiological compressive loading on 3D-embedded chondrocytes. To assess loading-induced changes in metabolites (e.g. small molecules representing the functional state of the cell) and proteome-wide patterns of post-translational modifications (i.e. phosphorylation), chondrocytes were encapsulated in physiologically stiff agarose, compressively loaded in tissue culture, and analyzed via liquid chromatography -- mass spectrometry (LC-MS). The results helped identify global and local biological patterns in the chondrocytes which are a direct result from mechanical loading. In addition, a novel mouse model that expresses cartilage specific bioluminescence was used to assess loading induced changes in vivo. The results from the mouse model allowed for in vivo validation and integration of the in vitro results from the metabolomic and phosphoproteomic results. To my knowledge, such research has never been done, and considerably expands the scientific knowledge of chondrocyte mechanotransduction.
Investigation of membrane tearing characterization and healing
(Montana State University - Bozeman, College of Engineering, 2011) Zignego, Donald Lee; Chairperson, Graduate Committee: Christopher H. M. Jenkins
As man's curiosity for deep space exploration increases, so does the demand for long duration space systems. To be able to explore deeper into space, a system is required in which little or no fuel is required for propulsion. Solar sails met this challenge by using solar photon momentum exchange for propulsion. Solar sails are large gossamer structures spanning as long as three football fields in width and length, but only microns in thickness. The main photon catching structure is constructed of thin polymeric membranes, which are quite susceptible to damage. Other applications for these polymeric membranes include flex circuits, and thermal control membranes. The tearing behaviors of these materials are vital in the design of these structures. In this study, the tear behaviors of two popular thin polymeric materials used in the space industry are explored; biaxially-oriented polyethylene terephthalate (Mylar) and Kapton. Tearing properties for the Mylar were experimentally determined using essential work of fracture methodology. Experiments were performed on DENT specimens with varying ligament lengths, and on three different thicknesses of Mylar: 25.4 micron (1 mil), 50.8 micron (2 mil), and 76.2 micron (3 mil). Specific essential work of fracture values were determined to be 37.027 kJ/m ², 36.974 kJ/m ², 36.853 kJ/m ² for the 25.4 micron, 50.8 micron, and 76.2 micron thick Mylar specimens, respectively. The specific essential work of fracture values were nearly identical for the three separate thicknesses, and therefore can be concluded that it is indeed a material property of the Mylar itself. Using biology as inspiration, the possibilities of self-healing in both the Mylar and Kapton are also analyzed. Analysis of the possibilities of self-healing was studied using an ultrasonic transducer. Specimens with an initial crack were created and strain or fracture energy values computed with and without healing. The Mylar's ability to resist tearing increased as much as 1300% in the healed specimens, and likewise as much as 950% increase for the Kapton. Tear tests were also performed at sub-zero temperatures to analyze the effects at space equivalent temperatures.