Quantifying Multi-Scale Architecture of Cardiac Tissues

项目总结/摘要 生物组织具有复杂的多尺度组织，它集成了多个组件， 在病理学中，真实常常是变化的。此外，据怀疑，改变的结构有助于损失 组织和器官的有效功能。例如，心肌的肌纤维组织是 在许多心脏病期间受到干扰，并且已知结构变化会影响收缩性和 电生理学然而，建筑在特定空间尺度上变化的机制 影响肌肉功能，例如收缩性，还没有很好地理解。其中一个最大的挑战是， 涵盖这些机制的是活肌肉组织的适应性。事实上，改变建筑， 一些长度尺度触发下游效应，该下游效应反映在一种蛋白质的表达水平的变化中。 各种基因，其中一些有助于收缩功能。因此，心脏的机械生物学 在许多方面，组织仍然是一个谜，在这个项目中，通过发现， 实验和建模工作，一些生物力学定律，控制之间的关系或- 组织和收缩性。在目标1中，我们将扩展对机械后果的理解 在某些组织中引发的生物学变化， 在确定横纹肌的结构-功能关系中，重要的是肌细胞的配准， eres。在目标2中，我们将优化目标1中开发的现有分析软件和代码，以了解 干细胞衍生的心脏组织的异质成熟性质。新的图像分析方法将 结合结构-功能模型来阐明心脏发育的机制。

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.