Biomechanical Regulation of Intranuclear Elastography and Gene Location in Single Cells

这笔拨款将用于研究人体细胞对机械力的反应。这项工作的结果将极大地推动科学进步和改善国民健康。机械生物学是一门试图解释细胞如何主动适应机械力的科学。了解细胞的机械生物学可以带来新的疗法来治疗由于衰老和疾病造成的损伤。细胞对力的反应有很多种方式，这通常涉及到细胞核，细胞核中含有定义我们遗传密码的DNA。然而，我们还不知道机械力是如何刺激细胞改变DNA的结构和位置的。该奖项支持基础研究，以测量细胞核中的基因表达及其如何随着施加的力而变化。这将揭示细胞在外力触发下改变其生物功能的机制。了解这一复杂的生物过程可能会为医学科学带来新的治疗和诊断方法。这个研究项目是多学科的，影响生物医学工程、成像、生物力学、细胞生物学和材料科学。该项目还将使包括儿童在内的代表性不足的群体广泛参与研究。预计这种推广将对科学和工程教育产生积极影响。本项目的目的是研究核基因表达的结构和生物力学调控，利用新的方法来测量活细胞中的弹性成像和基因定位。细胞核结构的复杂性和层级性是细胞核的特征，细胞核中蛋白质编码基因的表达模式受到多种因素的调控，包括染色质组织和运动的动力学。不幸的是，核内生物力学和基因位置如何与转录等复杂过程相关仍然没有很好的定义。我们的工作旨在为生物力学和力学生物学领域提供新的方法和知识，包括首次使用新的方法和数据来描述受生理相关条件挑战的单细胞细胞核的应变和材料特性的空间模式，直接证据与基因激活有关的基因定位和细胞刺激后的染色质力学，以及平台技术来更广泛地探索细胞核中的力学生物学机制。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 grant will support research about how the cells of our bodies react to mechanical forces. The results of this work will greatly advance progress in science and improvements in national health. Mechanobiology is a science that seeks to explain how cells actively adapt to mechanical forces. Understanding the mechanobiology of cells can lead to new therapies to treat damage due to aging and disease. There are many ways that cells react to force, which often involves the cell nucleus that contains the DNA defining our genetic code. However, we do not yet know how mechanical force stimulates the cell to alter its structure and position of DNA. This award supports fundamental research to measure gene expression in the cell nucleus and how it changes with applied forces. This will reveal mechanisms that cells use to alter their biological function triggered by force. Understanding this complex biological process may lead to new therapeutic and diagnostic approaches in medical science. This research project is multidisciplinary, and impacts the sciences of biomedical engineering, imaging, biomechanics, cell biology, and materials science. This project will also target broad participation of underrepresented groups in research, including children. This outreach is anticipated to positively impact education in science and engineering.The objective of this project is to study the structural and biomechanical regulation of nuclear gene expression using new methods to measure elastography and gene positioning in living cells. Structural complexity and hierarchy are hallmarks of the cell nucleus, and the expression patterns of protein-coding genes in the nucleus are regulated by multiple factors, including the dynamics of chromatin organization and movement. Unfortunately, how intranuclear biomechanics and gene position relate to complex processes like transcription are still not well defined. Our work aims to provide new methods and knowledge to biomechanics and mechanobiology communities, including first-of-its-kind methods and data describing spatial patterns of strain and material properties for nuclei of single cells challenged by physiologically-relevant conditions, direct evidence relating gene activation to gene location and chromatin mechanics following cell stimuli, and platform technologies to more broadly explore mechanisms of mechanobiology in the nucleus.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.