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

该学院早期职业发展（Career）奖支持研究单细胞-细胞粘附的机械行为特征。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。它们也会经历不同程度和速率的压力。目前，对细胞-细胞黏附的应变速率依赖行为缺乏了解。这对于在应变率谱中发挥作用的响应机制尤其正确。这些知识对于理解细胞-细胞粘连起重要作用的各种病理条件和发育缺陷至关重要。本研究项目将量化单细胞对的应力-应变关系。不同的拉伸应变率将被用来检查控制细胞-细胞粘附反应的过程。结果将阐明细胞骨架网络和细胞-细胞粘附的协调反应。补充外展计划将把实验室的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完成。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。本研究的具体目标是揭示单细胞-细胞粘附连接在受到不同应变速率的机械应变时的机械响应机制。人们普遍认为细胞骨架网络中的应力积累是应变速率相关的。因此，了解细胞骨架在不同应变速率下的应力松弛如何与增强细胞-细胞粘附相协调以防止多细胞结构的断裂是至关重要的。正在验证的中心假设是，在拉伸载荷下，细胞骨架重组和细胞-细胞粘附增强/破裂依赖于加载速率，并由细胞-细胞粘附时的机械传感分子驱动。两个研究目标，分别关注细胞骨架和细胞-细胞粘附，包括：1)检查细胞粘附-细胞骨架网络的速率依赖的应力松弛和张拉，以及2)检查细胞-细胞连接的速率依赖的增强，减少拉伸载荷下的破裂电位。通过这两个目标，将回答机械生物学中的一个基本问题：细胞-细胞粘附感知和响应的基本机械变量是力/应力或变形/应变，还是这些变量的速率变化？这些目标的成功完成将为开拓细胞-细胞粘附的应变速率依赖的机械行为的研究奠定坚实的基础，利用单个细胞-细胞粘附询问平台的独特能力。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 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.