Title: Predicting individual cardiomyocyte fiber organization in spatially constrained cells

Abstract: A functional, healthy heart relies on the coordination of architecture across multiple length scales and there is a need for models that predict myofibrillogenesis. Current predictive models for whole cardiomyocyte myofibrillogenesis have assumed that the dimensions of the myofibrils are significantly smaller than the dimensions of the cell. Consequently, their predictive power is limited in cases where the width or length of the cell is on the same length scale as that of the nucleus. We hypothesize that model predictions of the fiber distribution in highly elongated cells fail because the models do not consider the size and packing of individual fibers. They are also unable to accurately predict the placement of z-lines, whose registration can be a better indicator of tissue organization than actin placement alone. Our aim is to include these spatial scales and explore why their inclusion is essential in predicting self-assembly in elongated cells. Furthermore, we hope to be able to accurately predict the placement and registration of z-lines to study both tissue and cell organization.

We incorporated scaling terms into a current model of myofibrillogenesis, used the results to construct potential fiber networks for a given cell size and shape, and created a theoretical model to predict the placement of z-lines along each individual myofibril bundle within the network. The validity of each portion of our model is being tested using limiting cases and by comparing the model outputs to experimentally consistent data. By constructing our model in this way, we are able to explore a variety of dynamic relationships in cardiomyocyte myofibrillogenesis.