Cardiac-Cell Mechanics at the Single-Cell Level: Properties and Interactions

单细胞水平的心脏细胞力学：属性和相互作用

基本信息

批准号：
8306783
负责人：
Delphine Dean
金额：
$ 16.42万
依托单位：
CLEMSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8306783
关键词：
Actins Address Adult Affect Animals Antibodies Atomic Force Microscopy B-Lymphocytes Biochemistry Biological Assay Biomedical Engineering Cadherins Cardiac Cardiac Myocytes Cell Communication Cell Culture Techniques Cell Therapy Cell physiology Cells Cellular Structures Cellular biology Characteristics Coculture Techniques Collagen Complement Complex Computer Simulation Confocal Microscopy Connexins Coupling Cytoskeleton Data Defect Development Disease Educational workshop Electrical Engineering Engineering Equilibrium Extracellular Matrix Extracellular Matrix Proteins Fibroblasts Fibronectins Funding Future Gel Goals Heart Heart Diseases Image Imaging Techniques In Vitro Individual Injury Knowledge Laminin Measurement Measures Mechanical Stress Mechanics Mentors Microtubules Modeling Molecular Molecular Biology Motion Muscle Cells Myocardial Infarction Nature Pathologic Processes Pathology Pattern Physiological Processes Procedures Process Property Proteins Pump Rattus Regenerative Medicine Research Research Personnel Research Training Signal Transduction Solid South Carolina Stress Structure System Techniques Testing Theoretical model Time Tissue Engineering Tissues Touch sensation Traction Training Training Technics United States National Institutes of Health Universities Variant Work base cell type design experience in vivo mechanical behavior nanoindentation nanoscale polyacrylamide gels predictive modeling programs repaired scaffold skills three dimensional structure

项目摘要

This proposal describes a five-year training and research plan to broaden the Pi's electrical engineering background and help her gain experience in cardiac cell biology. To achieve this, the PI (Clemson University) will work closely with her mentors, Dr. Naren Vyavahare at Clemson University and Dr. Thomas Borg and Dr. Edie Goldsmith, at the University of South Carolina. The training plan includes 1) coursework in cell biology and biochemistry, 2) hands-on experimental technique training in cardiac cell culture and molecular biology assays, and 3) professional development activities through workshops and networking opportunities. The goal of this training to is allow the PI to gain the skills necessary to apply for independent NIH funding (e.g., R01) and to allow her to become a well-balanced biomedical engineering researcher. To complement the training, the PI proposes a research plan aimed at combining her engineering expertise with the cardiac cell biology techniques in which she will train. The complex interplay of cell function and mechanical stresses is important for many physiological and pathological processes, such as defects and diseases in mechanically active tissues like the heart. A solid understanding of this relationship would enable better design of in vitro constructs that could be used for tissue-engineered treatment of mechanically active tissues. Presently, the nature of these interactions is not fully understood, largely due to limitations in traditional single-cell mechanical measurement techniques. The proposed researchfocuses on understanding cardiac-cell mechanics and interactions as a function of the microenvironment. First, the mechanical properties of cardiomyocytes and fibroblasts as a function of the extracellular matrix will be assessed using atomic force microscopy. Then, the effect of cardiomyocyte-fibroblast interactions on cellular mechanics will be determined. Finally, structure-based cell-mechanics models will be built that will enable the use of data from imaging techniques to predict cardiac-cell mechanical properties. The long-term goal of this proposal is to better understand the mechanical coupling of cardiac cells. This understanding is critical for building effective micro- to macroscale models of cardiac tissue function, which is the key for developing in vivo repair strategies based on regenerative medicine.

该提案描述了一个为期五年的培训和研究计划，以扩大 Pi 的电气功能工程背景并帮助她获得心脏细胞生物学的经验。为了实现这一目标，PI （克莱姆森大学）将与她的导师克莱姆森大学的 Naren Vyavahare 博士和南卡罗来纳大学的托马斯·博格和伊迪·戈德史密斯博士。培训计划包括1）细胞生物学和生物化学课程，2）心肌细胞实践实验技术培训培养和分子生物学测定，以及 3) 通过研讨会和建立联系的机会。本次培训的目的是让 PI 获得申请所需的技能独立的 NIH 资助（例如 R01）并让她成为一名均衡的生物医学工程师研究员。为了补充培训，PI 提出了一项研究计划，旨在将她的工程她将接受培训的心脏细胞生物学技术方面的专业知识。细胞之间复杂的相互作用功能和机械应力对于许多生理和病理过程很重要，例如心脏等机械活动组织的缺陷和疾病。对这种关系有深刻的理解将能够更好地设计可用于组织工程治疗的体外结构机械活性组织。目前，这些相互作用的本质尚未完全理解，很大程度上是由于传统单细胞机械测量技术的局限性。拟议的研究重点是了解心脏细胞力学和相互作用作为微环境的函数。首先，心肌细胞和成纤维细胞的机械特性作为细胞外基质的函数将是使用原子力显微镜进行评估。然后，心肌细胞-成纤维细胞相互作用对细胞的影响力学将被确定。最后，将建立基于结构的细胞力学模型，这将使使用成像技术的数据来预测心脏细胞的机械特性。该提案的长期目标是更好地了解心脏细胞的机械耦合。这种理解对于建立有效的心脏组织功能的微观到宏观模型至关重要，这是开发基于再生医学的体内修复策略的关键。