Analysis of Physical Mechanisms in Cell Adhesion

描述（由申请人提供）： 控制炎症是提高工程组织和移植组织活力的关键。考虑到这一点，我们的工作阐明了促进中性粒细胞向炎症组织募集的膜重塑事件。第一个目的是研究粘附调节的物理机制，包括整合素和选择素受体的流动性和定位，使用光漂白后的荧光恢复（FRAP），全内反射荧光（TIRF）和图像互相关光谱（ICCS）。这些工具的互补性将评估受体的位置和流动性，具有上级的信心和准确性超过所有以前的工作。采用这些技术与药物治疗，第二个目的是测试一个假设，即粘附分子重新分布与激活的中性粒细胞，因为短暂的细胞骨架释放的横向流动性增加。第三个目的是检查迁移性中性粒细胞。使用定量显微镜和生化处理，允许同时可视化的表面受体和细胞骨架，这一目标假设，高整合素流动性和低选择素流动性的迁移的固有特征和相关的基本细胞骨架结构。

DESCRIPTION (provided by applicant): Controlling inflammation is key to improving the viability of engineering and transplanted tissues. With this in mind, our work elucidates the membrane remodeling events that facilitate recruitment of neutrophils to inflamed tissues. The first aim examines the physical mechanisms of adhesion regulation including mobility and localization of integrin and selectin receptors using fluorescence recovery after photobleaching (FRAP), total internal reflection fluorescence (TIRF), and image cross-correlation spectroscopy (ICCS). The complementary nature of these tools will assess the position and mobility of receptors with superior confidence and accuracy over all previous work. Employing these techniques with pharmacological treatments, the second aim tests a hypothesis that adhesion molecules redistribute with increased lateral mobility on activated neutrophils because of transient cytoskeletal release. The third aim examines migratory neutrophils. Using quantitative microscopy and biochemical processing that allows simultaneous visualization of surface receptors and cytoskeleton, this aim hypothesizes that high integrin mobility and low selectin mobility are inherent features of migration and correlated with underlying cytoskeletal structure.