UC Irvine

Through a variety of mechanisms, a healthy heart is able to regulate its structure and dynamics across multiple length scales. Disruption of these mechanisms can have a cascading effect, resulting in severe structural and/or functional changes that permeate across different length scales. Due to this hierarchical structure, there is interest in understanding how the components at the various scales coordinate and influence each other. While there has been much progress at the molecular scale, there is a growing need for theoretical models to address interactions at the cellular and subcellular scales. In particular, understanding the mechanisms guiding the formation and organization of the cytoskeleton in individual cardiomyocytes can aid tissue engineers in developing functional cardiac tissue.

In this dissertation, we developed computational models which integrate interactions at both the cellular and subcelluar scale to enhance our understanding of how cardiomyocytes self-assemble at different length scales. Experimental data, which consisted of single cell cardiomyocytes having fixed area but variable aspect ratio, was used to test and validate our models. Cells were analyzed for structural consistency and contractility using estab- lished metrics. The metrics where then applied to our model simulations for comparison. We demonstrated that our model simulations are capable of reproducing the stochasticity observed in experimental cells at different length scales while also mimicking structural consistency. In addition to recreating known patterns present in the experimental cells, our models have provided insight towards possible mechanisms that can be explored by experi- mentalists.