CAREER: Characterization of the Strain Rate-Dependent Mechanical Behavior of the Cell-Cell Adhesion Interface

这个教师早期职业发展（CAREER）奖支持研究，以表征单细胞-细胞粘附的机械行为。细胞-细胞粘附将细胞整合到组织中。它们在细胞外环境和细胞之间传递信号。他们也经历不同程度和速度的紧张。目前，对细胞-细胞粘附的应变率依赖性行为缺乏了解。这是特别真实的响应机制在整个频谱的应变率。这些知识对于理解细胞间粘附起重要作用的各种病理条件和发育缺陷至关重要。该研究项目将量化单个细胞对的应力-应变关系。不同的拉伸应变率将被用来检查的过程中，支配细胞-细胞粘附的反应。这些结果将阐明细胞骨架网络和细胞-细胞粘附的协调反应。补充推广计划将把实验室创新转化为幼儿的学习机会。这将通过K-12学生的互动教育平台来实现。该职业奖还将通过实验室指导计划为本科生提供研究机会。研究的具体目标是揭示单细胞-细胞粘附连接在不同应变率的机械应变下的力学响应机制。一般认为细胞骨架网络中的应力积累是应变率依赖性的。因此，了解不同应变率下细胞骨架的应力松弛如何与细胞-细胞粘附的增强协调以防止多细胞结构断裂是至关重要的。正在测试的中心假设是，在拉伸负荷下，细胞骨架重组和细胞-细胞粘附增强/破裂是负荷率依赖性的，并由细胞-细胞粘附处的机械传感分子驱动。分别关注细胞骨架和细胞-细胞粘附的两个研究目标包括：1）检查细胞粘附-细胞骨架网络的速率依赖性应力松弛和张紧，以及2）检查细胞-细胞连接的速率依赖性增强，其降低拉伸载荷下的断裂潜力。通过这两个目标，机械生物学中的一个基本问题将得到回答：细胞-细胞粘附感测和响应的基本机械变量是什么，力/应力或变形/应变，或者这些变量的变化率？该项目的成功完成将为利用单细胞-细胞粘附研究平台的独特功能，开创细胞-细胞粘附的应变率依赖性力学行为的研究奠定坚实的基础。该奖项反映了NSF的法定使命，并通过使用基金会的智力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 Faculty Early Career Development (CAREER) award supports research to characterize the mechanical behavior of single cell-cell adhesions. Cell-cell adhesions integrate cells into tissues. They relay signals between the extracellular environment and cells. They also experience strains of different magnitudes and rates. Currently, there is a lack of understanding about the strain rate-dependent behavior of the cell-cell adhesion. This is particularly true of the response mechanisms at play across the spectrum of strain rates. This knowledge is critical in understanding various pathological conditions and developmental defects where cell-cell adhesions play a significant role. This research project will quantify the stress-strain relationship of a single cell pair. Different tensile strain rates will be used to examine the process that governs the responses of the cell-cell adhesions. The results will elucidate the coordinated response from the cytoskeleton network and cell-cell adhesions. The complementary outreach program will translate laboratory innovations into learning opportunities for young kids. This will be accomplished through interactive educational platforms for K-12 students. This CAREER award will also provide research opportunities for undergraduate students via a laboratory mentoring program. The specific goal of the research is to uncover the mechanisms governing the mechanical response of single cell-cell adhesion junctions when they are subjected to mechanical strains of different strain rates. It is generally accepted that stress accumulation in the cytoskeleton network is strain rate-dependent. Thus, it is critical to understand how stress relaxation by the cytoskeleton under different strain rates coordinates with the enhancement of cell-cell adhesion to prevent fracture of multicellular structures. The central hypothesis being tested is that under tensile loading cytoskeleton reorganization and cell-cell adhesion enhancement/rupture are loading rate-dependent and driven by mechanosensing molecules at the cell-cell adhesion. Two research objectives, focusing on the cytoskeleton and the cell-cell adhesion, respectively, include: 1) examine the rate-dependent stress relaxation and tensioning of the cell adhesion-cytoskeleton network, and 2) examine the rate-dependent enhancement of cell-cell junctions that reduces rupture potential under tensile loads. Through the two objectives, one of the fundamental questions in mechanobiology will be answered: what fundamental mechanical variables do cell-cell adhesions sense and respond to, force/stress or deformation/strain, or the rate change of these variables? The success in completion of the objectives will build a solid foundation for pioneering the study of the strain rate-dependent mechanical behavior of cell-cell adhesions, leveraging the unique capability of a single cell-cell adhesion interrogation platform.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.