Abstract
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 cascad- ing effect, resulting in severe structural and/or functional changes that permeate across different length scales. Due to this hierarchical structure, there is interest in understand- ing how the components at the various scales coordinate and influence each other. However, much is unknown regarding how myofibril bundles are organized within a densely packed cell and the influence of the subcellular components on the architecture that is formed. To elucidate potential factors influencing cytoskeletal development, we proposed a compu- tational model that integrated interactions at both the cel- lular and subcelluar scale to predict the location of indi- vidual myofibril bundles that contributed to the formation of an energetically favorable cytoskeletal network. Our model was tested and validated using experimental metrics derived from analyzing single cell cardiomyocytes. We demonstrated that our model-generated networks were capable of repro- ducing the variation observed in experimental cells at different length scales as a result of the stochasticity inher- ent in the different interaction between the various cellu- lar components. Additionally, we showed that incorporat- ing length-scale parameters resulted in physical constraints that directed cytoskeletal architecture towards a structurally consistent motif. Understanding the mechanisms guiding the formation and organization of the cytoskeleton in individual cardiomyocytes can aid tissue engineers towards developing functional cardiac tissue.
Self-assembly in soft matter with multiple length scales
