Mapping Elastic Properties of Complex Biological Tissue

大多数生物组织是相当复杂的结构，在微观和纳米尺度上具有材料性质和结构的不均匀性。组织的结构和功能的详细表征将通过绘制组织的弹性特性与微观分辨率服务。原子力显微镜（AFM）是构建这种图谱的理想工具，它可以在组织感兴趣的区域内的大量点上进行纳米压痕测试，并使用适当的数学模型在每个点提取所需的弹性参数。这种程序通常需要分析数百或数千个数据集。如果没有自动化，这是一个非常繁琐的过程，这阻碍了它对生物组织（如软骨）弹性特性的详细映射的使用。我们正在构建一个强大的自动化工具，它将允许在任何分辨率下进行例行的弹性映射。目的有两个：首先，我们想在微观结构水平上研究和比较天然软骨和组织工程软骨以及其他聚合物凝胶样组织的弹性特性。同时，我们研究了更简单的人工凝胶，我们增加了更多的复杂性（增加了各种分子成分和各种不均匀性），并将AFM与宏观和渗透测量相结合，努力阐明决定此类组织弹性行为的因素。其次，弹性图谱构建自动化软件的开发将创造一种工具，可以并且将被内部合作者广泛用于各种项目，例如与NIDCD合作者一起研究内耳膜的弹性特性，以及测量支持的脂质双层的材料特性。

Most biological tissues are rather complex structures with inhomogeneities in material properties and structure at micro- and nanoscopic scales. Detailed characterization of the structure and function of tissues would be served by mapping elastic properties of the tissue with microscopic resolution. The atomic force microscope (AFM) is an ideally suited tool for constructing such maps by doing nano-indentation tests at a large set of points throughout a domain of interest on the tissue and using appropriate mathematical models to extract the desired elastic parameters at each point. Such procedure typically requires analysis of hundreds or thousands of data sets. Without automation, this is a very tedious process which is hindering its use for detailed mapping of elastic properties of biological tissue such as cartilage. We are building a powerful automation tool that will allow routine elasticity mapping at any resolution. The goal is twofold: First we want to investigate and compare the elastic properties of natural and tissue-engineered cartilage and other polymer gel-like tissues at the microstructure level. At the same time we investigate simpler artificial gels to which we add ever more complexity (adding various molecular components and various inhomogeneities) and use the AFM in conjunction with macroscopic and osmotic measurements in an effort to elucidate the factors determining the elastic behavior of such tissues. Second, development of the automation software for elastic map construction will create a tool that can and will be used widely by intramural collaborators in a variety of projects, such as the one with NIDCD collaborators on investigating the elastic properties of the tectorial membrane in the inner ear, and the measurement of material properties of supported lipid bilayers.