Study of Dynamical Mechanical Properties of Pericellular Layer

这个项目将开发新的工具，在纳米尺度上研究单个生物细胞的物理特性。覆盖在大多数细胞细胞体上的细胞刷状部分的性质仍然未知。这很有趣，因为众所周知，这一刷层的生物学变化与许多人类疾病有关，如癌症、心血管疾病，甚至衰老。这项工作将支持实验和理论方法的发展，以研究这种刷层在单个细胞上的物理特性。这些开发的方法将被应用于研究最令人费解的生物之一裸鼹鼠的细胞，裸鼹鼠寿命长，对癌症有很强的抵抗力。这项对刷层年龄相关变化的研究可能最终揭示与衰老相关的某些疾病（包括癌症）患病率呈指数增长的机制。这项多学科的工作将结合来自三个不同机构的物理学、工程学和生物学研究人员的专业知识。这个由多所大学参与的项目将有助于扩大代表性不足的群体参与研究，并对工程教育产生积极影响。原子力显微镜将用于开发一种新的高分辨率实验方法来测量细胞周围细胞周层的动态力学特性。该项目的方法源于一种新的技术，傅里叶变换动态力学分析，一种快速的高分辨率定量方法将允许在亚细胞水平上测量频率相关的存储和损耗模量。这些机械性能被认为是非常重要的。因此，预计将需要先进的力学模型，如各种粘弹性和孔弹性接触模型。这些模型将被研究并与实验结果进行比较，以了解细胞周围刷层的物理和力学性质。研究小组将利用该方法研究裸鼹鼠成纤维细胞细胞周层的机制。这些动物与其他啮齿类动物如豚鼠、大鼠、小鼠之间的差异将被研究，以了解裸鼹鼠与正常衰老的啮齿动物相比的衰老相关变化。特定多糖的重要性，如透明质酸，对细胞周围层的力学将进行研究。它将填补我们对裸鼹鼠细胞周围层的具体力学特征的知识空白，并有助于癌症和长寿的物理学。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This project will develop novel tools to study physical properties of individual biological cells at the nanoscale. The properties of a brush-like part of cells that covers the cell body of most cells have remained unknown. This is interesting because it is known that the biological changes in this brush layer are correlated with many human diseases, like cancer, cardiovascular diseases, and even aging. This work will support the development of experimental and theoretical methods to study the physical properties of this brush layer on individual cells. The developed methods will be applied to study cells of one of the most puzzling creatures, naked mole rats, which are long-lived and highly resistant to cancer. This study of age-related changes in the brush layer may eventually shed light on the mechanisms responsible for the exponential increase in the prevalence of certain diseases (including cancer) associated with aging. This multidisciplinary work will combine expertise from physics, engineering, and biology of researchers from three different institutions. This multi-university project will help broaden participation of underrepresented groups in research and have a positive impact on engineering education.Atomic force microscopy will be used to develop a novel high-resolution experimental method to measure the dynamical mechanical properties of the pericellular layer surrounding cells. The project's approach arises from a novel technique, Fourier-transform dynamical mechanical analysis, a fast high-resolution quantitative method will allow for measuring frequency-dependent storage and loss moduli at the subcellular level. These mechanical properties are expected to be highly nontrivial. Therefore, it is expected that advanced mechanical models, such as various viscoelastic and poroelastic contact models, will be necessary. These models will be investigated and compared with the experimental results to understand the physical and mechanical nature of the pericellular brush layer. The research team will apply the developed methods to study the mechanics of the pericellular layer of fibroblasts of naked mole rats. The difference between these animals and other rodents like the guinea pig, rats, mice will be investigated to learn the aging-related changes in naked mole rats in comparison with regular aging rodents. The importance of particular polysaccharides, such as hyaluronic acid, for the mechanics of the pericellular layer will be studied. It will fill the gap in our knowledge on the specific features of mechanics of the pericellular layer of naked mole rats and contribute to the physics of cancer and longevity.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.