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

该学院早期职业发展(CALEAR)奖支持研究单细胞-细胞粘连的机械行为。细胞间的粘连将细胞整合成组织。它们在细胞外环境和细胞之间传递信号。他们还经历了不同程度和程度的压力。目前，对细胞-细胞黏附的应变率依赖行为缺乏了解。这一点在不同应变率范围内发挥作用的反应机制尤其如此。这一知识对于理解细胞间黏附起重要作用的各种病理条件和发育缺陷至关重要。这项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控制细胞-细胞黏附反应的过程。这些结果将阐明细胞骨架网络和细胞-细胞黏附的协调反应。这一互补的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。这一职业奖项还将通过实验室指导计划为本科生提供研究机会。这项研究的具体目标是揭示当单细胞-细胞黏附连接受到不同应变率的机械应变时，它们的机械反应机制。人们普遍认为细胞骨架网络中的应力积累是应变率相关的。因此，了解细胞骨架在不同应变率下的应力松弛如何与细胞-细胞黏附的增强相协调，以防止多细胞结构的断裂是至关重要的。正被检验的中心假设是，在拉伸载荷下，细胞骨架重组和细胞-细胞黏附的增强/破裂是由细胞-细胞黏附处的机械传感分子驱动的，并且依赖于载荷率。分别针对细胞骨架和细胞-细胞黏附的两个研究目标包括：1)研究细胞黏附-细胞骨架网络的速率依赖的应力松弛和拉伸；2)研究细胞-细胞连接在拉伸载荷下降低破裂可能性的速率依赖的增强。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-细胞粘连感知和响应哪些基本的力学变量，力/应力或变形/应变，或者这些变量的速率变化？这些目标的成功完成将为利用单个细胞-细胞黏附询问平台的独特能力率先研究细胞-细胞黏附的应变率相关力学行为奠定坚实的基础。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 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.