Fast and High-resolution Dynamic Mechanical Spectroscopy of Biological Cells

动态力学光谱允许在不同的速度下测量材料的机械性能。它是研究软材料如聚合物的一种流行技术。然而，由于一些固有的问题，这种技术尚未扩展到研究生物细胞的特性。除了基本的兴趣，细胞力学的研究在理解各种疾病中细胞的机械变化方面产生了实际影响，如癌症，疟疾，阿尔茨海默病，甚至衰老。但大多数 对它们的静态特性进行了电池研究。虽然细胞的动态力学性质的变化预计会丰富得多，但现有的测量细胞动态性质的尝试非常有限，并且结果存在争议。该奖项支持基础研究，为开发新的定量技术提供所需的知识，以进行细胞的动态力学测量。 这种新方法有可能彻底改变细胞力学的研究。总的来说，它也将在纳米尺度上为生物材料和纳米复合材料的力学研究带来新的维度。它将把知识库扩大到以前无法达到的分辨率。翻译部分将包括癌细胞生物力学的研究。这项应用可以为纳米机械在医疗保健中的应用奠定基础，通过早期发现癌症节省数十亿美元，使美国社会受益。这项研究将结合联合收割机物理学、生物学、电子学和纳米技术。这种多学科的方法将有助于扩大研究中代表性不足的群体的参与，并对机械和生物医学工程教育产生积极影响。动态力学光谱学处理材料的存储和损耗模量，这是模型依赖性最小的量。虽然这种方法是软材料的标准方法，但测量时间过长和分辨率低使其无法在生物细胞上获得可靠的模量。此外，细胞是复杂的复合对象。本研究将联合收割机快速傅立叶光谱与原子力显微镜相结合，提高动态力学光谱的速度和空间分辨率。与现有方法相比，预计速度将提高100倍以上，分辨率将提高100倍以上。 研究小组将应用这种方法来开发适当的粘弹性细胞模型，特别是考虑到细胞周刷，这是一种重要的细胞器，其动态力学特性尚未被发现。所获得的知识将应用于研究人类宫颈癌和乳腺癌细胞的生物力学。

Dynamic mechanical spectroscopy allows measuring mechanical properties of materials at different speeds. It is a popular technique for studying soft material such as polymers. However, because of several intrinsic problems, this technique has not been extended to study the properties of biological cells as of yet. Besides fundamental interest, the study of cell mechanics makes a practical impact in understanding mechanical changes of cells in various diseases, like cancer, malaria, Alzheimer, and even aging. However, most cell studies were done for their static properties. While the changes in dynamic mechanical properties of cells are expected to be much richer, the existing attempts to measure cell dynamic properties have been very limited, and the results are controversial. This award supports fundamental research to provide knowledge needed for the development of a new quantitative technique to perform dynamic mechanical measurements of cells. The new method has the potential to revolutionize the study of cell mechanics. In general, it will also bring a new dimension to the study of the mechanics of biomaterials and nanocomposites at the nanoscale. It will expand the knowledge base to a scale of resolutions previously inaccessible. A translational part will include investigation of biomechanics of cancer cells. This application can build the foundation for nanomechanical applications in healthcare, which can benefit the U.S. society by saving billions of dollars through the early detection of cancer. The research will combine physics, biology, electronics, and nanotechnology. This multi-disciplinary approach will help broaden participation of underrepresented groups in research and positively impact mechanical and biomedical engineering education.Dynamic mechanical spectroscopy deals with the storage and loss moduli of materials which are the least model dependent quantities. While this method is standard for soft material, excessive time of measurements and low resolution preclude its use from obtaining reliable moduli on biological cells. In addition, cells are complex composite objects. This research will combine fast Fourier spectroscopy and atomic force microscopy to improve the speed and spatial resolution of dynamic mechanical spectroscopy. The improvement is expected to be more than 100x in speed and 100x in the resolution compared to the existing methods. The research team will apply this method to develop an appropriate viscoelastic cell model, in particular, taking into account pericellular brush, an important cellular organelle which dynamical mechanical properties are yet to be discovered. The obtained knowledge will be applied to study biomechanics of human cervical and breast cancer cells.