Date of Award
Master of Science (MS)
Because of the complexity of the in vivo environment, much physiological and pathological understanding of the human body is obtained through cell culture. To gain clinically relevant knowledge, having a cell culture model that mimics the corresponding in vivo tissue would be advantageous. For example, when studying the mechanical and electrical coupling between cardiac cells, imitating in vivo cellular morphology correlates with improved electrical coupling. This has applications within drug screening; by being able to test for cardiotoxicity with a cell culture model, this reduces the resources needed to screen pharmaceuticals for negative side effects. In conventional cardiomyocyte culture, cells spread randomly and express irregular, star-like morphology without forming in vivo-like structures. The purpose of this aim was to utilize microfabricated features such as wrinkles on polydimethylsiloxane (PDMS) and examine the effects of substrate topography on cardiomyocyte morphology and function. Of the substrate topographical parameters that result in optimal cellular alignment, we evaluate the electrical cohesiveness of these cell culture models via cellular calcium transients. Mammalian cardiomyocytes use the calcium-induced calcium release (CICR) pathway to induce calcium transients that are integral to the excitation-contraction cycle. Their efficiency in this is an indication of their electrophysiological maturity. Due to the intimate dynamics between physical and functional maturity, we examined how substrate topography affects the ability of cultured neonatal cardiomyocytes to cycle calcium ions in response to external stimulation.
Yu, Tiffany, "Microfabricated Substrate to Achieve In Vivo-Like Cardiomyocyte Morphology and Electrical Propagation in Neonatal Cell Culture" (2019). All Theses. 3219.