Study of Dynamical Mechanical Properties of Pericellular Layer

该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性质。覆盖大多数细胞胞体的刷状细胞部分的特性仍不清楚。这很有趣，因为众所周知，这一刷层中的生物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，以研究单个细胞上这种刷层的物理性质。开发的方法将用于研究最令人费解的生物之一--裸鼠的细胞，这种动物寿命长，对癌症具有高度抵抗力。这项关于刷毛层与年龄相关的变化的研究最终可能揭示与衰老相关的某些疾病(包括癌症)患病率呈指数级增长的机制。这项多学科的工作将结合来自三个不同机构的研究人员的物理、工程和生物学专业知识。这一多大学项目将有助于扩大未被充分代表的群体参与研究，并对工程教育产生积极影响。原子力显微镜将开发一种新的高分辨率实验方法，以测量细胞周围细胞周层的动态力学性质。该项目的方法源于一种新技术--傅里叶变换动态力学分析，这是一种快速、高分辨率的定量方法，将允许在亚细胞水平上测量与频率相关的存储和损耗模数。预计这些机械性能将非常重要。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相比较，以了解细胞周刷状层的物理和力学性质。该研究小组将应用开发的方法来研究裸鼠成纤维细胞细胞周层的力学。这些动物与其他啮齿动物如豚鼠、大鼠、小鼠的区别将被调查，以了解裸鼠与正常衰老啮齿动物相比的衰老相关变化。特定的多糖，如透明质酸，对于细胞周层的机制的重要性将被研究。它将填补我们在裸鼠细胞周层力学的具体特征方面的知识空白，并为癌症和寿命的物理学做出贡献。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.