Quantifying Multi-Scale Architecture of Cardiac Tissues

量化心脏组织的多尺度结构

• 批准号: 10217763
• 负责人: Anna Grosberg
• 金额: $ 7.14万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-20 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10217763
• 关键词: Address; Architecture; Biological; Biological Assay; Biomechanics; Cardiac; Cardiac Myocytes; Cardiac development; Cells; Code; Computer software; Data; Data Analyses; Disease; Effectiveness; Electrophysiology (science); Engineering; Experimental Models; Gene Expression; Generations; Genes; Geometry; Goals; Health; Heart; Heart Diseases; Heterogeneity; Image; Image Analysis; Implant; Laws; Length; Measures; Mechanics; Methods; Modeling; Muscle; Muscle function; Myocardium; Myofibrils; Nature; Organ; Outcome; Pathologic; Pathology; Patients; Pharmacology; Production; Pump; Sampling; Sarcomeres; Stress; Striated Muscles; Structure; Structure-Activity Relationship; Techniques; Time; Tissue Engineering; Tissues; Work; automated image analysis; cardiac tissue engineering; heart function; induced pluripotent stem cell; response; second harmonic; single-cell RNA sequencing; stem cells; tool

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.

项目概要/摘要 生物组织具有复杂的多尺度组织，集成了多个组件，而这个架构师- 此外，人们怀疑建筑会导致损失。 组织和器官的有效功能例如，心肌的肌原纤维组织是。 许多心脏病期间都会受到干扰，并且已知结构变化会影响收缩力和 然而，建筑在特定空间尺度上变化的机制。 影响肌肉的功能，例如收缩性，目前还没有被很好地理解。 事实上，覆盖这些机制的是活体肌肉组织的适应性，改变其结构。 某些长度尺度会触发下游效应，反映在a的表达水平的变化上 多种基因，其中一些有助于收缩功能，因此是心脏的机械生物学。 组织在许多方面仍然是一个谜，这个项目将通过发现、通过 实验和建模工作，一些控制或-之间关系的生物力学定律 在目标 1 中，我们将扩展对机械后果的理解。 通过探索某些组织中引发的生物变化是否是其中一种机制 在确定横纹肌结构功能关系中重要的是肉瘤的记录 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 新的图像分析方法将是干细胞来源的心脏组织的异质成熟性质。 结合结构功能模型阐明心脏发育背后的机制。