Mapping Elastic Properties of Complex Biological Tissue

大多数生物组织都是相当复杂的结构，材料性质和结构在微观和纳米尺度上都是不均匀的。通过用显微分辨率绘制组织的弹性属性图，可以对组织的结构和功能进行详细的描述。原子力显微镜(AFM)是构建这种地图的理想工具，它通过在组织上感兴趣的区域中的大量点进行纳米压痕测试，并使用适当的数学模型来提取每个点所需的弹性参数。这样的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，阻碍了它对软骨等生物组织弹性特性的详细绘制。我们正在构建一个强大的自动化工具，该工具将允许在任何分辨率下进行常规弹性映射。我们的目标有两个：首先，我们希望在微观结构水平上研究和比较天然和组织工程软骨以及其他聚合物凝胶样组织的弹性性质。与此同时，我们研究了更简单的人造凝胶，我们在其中添加了更多的复杂性(添加了各种分子成分和各种不均匀)，并使用AFM结合宏观和渗透测量，努力阐明决定此类组织弹性行为的因素。其次，弹性地图构建自动化软件的开发将创建一个能够并将被各种项目的内壁合作者广泛使用的工具，例如与NIDCD合作者研究内耳覆盖膜的弹性性质的工具，以及所支持的脂质双层的材料性质的测量。

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.