Study of Dynamical Mechanical Properties of Pericellular Layer

细胞周层动态力学性能研究

• 批准号: 2224708
• 负责人: Igor Sokolov
• 金额: $ 64.87万
• 依托单位: Tufts University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2224708&HistoricalAwards=false
• 关键词: Study; Dynamical; Mechanical; Properties; Pericellular

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.

该项目将开发新的工具来研究纳米级的单个生物细胞的物理特性。覆盖大多数细胞细胞体的细胞的刷状部分的特性仍然未知。这很有趣，因为众所周知，该刷层中的生物学变化与许多人类疾病（如癌症，心血管疾病，甚至衰老）相关。这项工作将支持开发实验和理论方法，以研究该刷子对单个细胞的物理特性。开发的方法将应用于研究最令人困惑的生物之一的细胞，即长期寿命且对癌症具有高度抵抗力的裸鼠大鼠。这项针对年龄相关的刷子层变化的研究最终可能阐明了导致某些疾病患病率（包括癌症）的指数增加的机制。这项多学科工作将结合来自三个不同机构的研究人员的物理，工程和生物学的专业知识。这个多元大学项目将有助于扩大代表性不足的小组在研究中的参与，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型的高分辨率实验方法，以测量周围细胞周围细胞的动力学机械性能。该项目的方法源于一种新型技术，傅立叶变换动力学分析，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依赖性的存储和损耗模量。这些机械性能预计将是高度不平凡的。 因此，预计将需要先进的机械模型，例如各种粘弹性和毛弹性接触模型。这些模型将进行研究，并将其与实验结果进行比较，以了解周围细胞刷层的物理和机械性质。研究团队将应用开发的方法来研究裸mole大鼠成纤维细胞周围层的力学。这些动物与其他啮齿动物（如豚鼠，大鼠，小鼠）之间的差异将被研究以学习与常规衰老啮齿动物相比，裸鼠大鼠与衰老相关的变化。将研究特定多糖（例如透明质酸）对细胞层的力学的重要性。它将填补我们对裸痣大鼠周围细胞周围层的特定特征的知识，并有助于癌症和长寿物理学。该奖项反映了NSF的法定任务，并被认为是通过基金会的评估来支持的，并被认为是值得的。智力优点和更广泛的影响审查标准。