Project Summary/Abstract Biological tissues have intricate multi-scale organizations integrating multiple component, and this architec- ture is often changed in pathology. Moreover, it is suspected that altered architecture contributes to loss of efficient functionalities in tissues and organs. For instance, the heart muscle's myofibril organization is disturbed during many heart diseases, and structural changes are known to impact both contractility and electrophysiology. However, the mechanisms by which architectural changes at a specific spatial scales impact muscle functionality, such as contractility, are not well understood. One of the big challenges in dis- covering these mechanisms is the adaptability of living muscle tissue. Indeed, changing the architecture at some length scales triggers a downstream effect that is reflected in a change to the expression levels of a variety of genes some of which contribute to the contraction function. Thus the mechanobiology of cardiac tissue remains, in many aspects, a mystery, which is to be address in this project by discovering, through experimental and modeling work, some of the biomechanical laws that control the relationship between or- ganization and contractility. In Aim 1, we will expand the understanding of the mechanical consequences of the biological changes triggered in some tissues by pursuing exploring if one of the mechanisms that is important in determining the structure-function relationship in striated muscle is the registration of sarcom- eres. In Aim 2, we will optimize existing analysis software and codes developed in Aim 1 to understand the heterogenous maturation nature of stem-cell derived cardiac tissues. New image analysis methods will be combined with structure-function model to elucidate the mechanisms behind cardiac development.