Fast and High-resolution Dynamic Mechanical Spectroscopy of Biological Cells

动态机械光谱学可以测量不同速度下材料的机械性能。这是一种研究聚合物等软材料的流行技术。然而，由于一些固有的问题，这项技术到目前为止还没有扩展到研究生物细胞的性质。除了基本的兴趣之外，细胞力学的研究在理解各种疾病中细胞的机械变化方面也有实际影响，如癌症、疟疾、阿尔茨海默氏症，甚至衰老。然而，大多数细胞研究都是针对它们的静态特性进行的。虽然细胞动态力学性质的变化预计会更加丰富，但现有的测量细胞动态性质的尝试一直非常有限，结果存在争议。该奖项支持基础研究，以提供开发新的定量技术所需的知识，以执行细胞的动态机械测量。这种新方法有可能给细胞力学的研究带来革命性的变化。总的来说，这也将为生物材料和纳米复合材料在纳米尺度上的力学研究带来新的维度。它将把知识库扩大到以前无法获取的决议范围。翻译部分将包括对癌细胞生物力学的研究。这一应用可以为纳米机械在医疗保健中的应用奠定基础，通过早期发现癌症可以节省数十亿美元，从而造福美国社会。这项研究将结合物理学、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未被充分代表的群体在研究中的参与，并对机械和生物医学工程教育产生积极的影响。动态机械光谱学研究的是材料的储存和损失模数，它们是最小的模型依赖量。虽然这种方法是软材料的标准方法，但过长的测量时间和低分辨率使其无法在生物细胞上获得可靠的模数。此外，单元格是复杂的复合对象。本研究将快速傅立叶光谱分析与原子力显微镜相结合，提高动态力学光谱分析的速度和空间分辨率。与现有方法相比，速度和分辨率有望提高100倍以上。研究小组将应用这种方法来开发合适的粘弹性细胞模型，特别是考虑到细胞周刷，这是一种尚未发现动态力学特性的重要细胞器。所获得的知识将用于研究人宫颈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.