Analysis of Physical Mechanisms in Cell Adhesion

细胞粘附的物理机制分析

• 批准号: 6935087
• 负责人: THOMAS R GABORSKI
• 金额: $ 4.17万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6935087
• 关键词: cell adhesion; cell motility; clinical research; cytoskeletal proteins; fluorescence microscopy; fluorescence recovery after photobleaching; human subject; integrins; leukocyte activation /transformation; neutrophil; predoctoral investigator; protein structure function; selectins; spectrometry

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.

描述（由申请人提供）： 控制炎症是改善工程和移植组织的生存能力的关键。考虑到这一点，我们的工作阐明了膜重塑事件，这些事件促进了中性粒细胞募集到发炎的组织。第一个目的检查了粘附调节的物理机制，包括光漂白后的荧光回收（FRAP），总内反射荧光（TIRF）和图像互相关光谱（ICC），包括整合素和选择蛋白受体的定位。这些工具的互补性将在所有以前的工作中以优越的信心和准确性评估受体的位置和流动性。第二个目标通过药理治疗采用这些技术，检验了一个假设，即由于短暂的细胞骨架释放，粘附分子在激活的中性粒细胞上重新分布，横向迁移率增加。第三目检查迁移性嗜中性粒细胞。使用定量显微镜和生化加工，允许同时可视化表面受体和细胞骨架，该目标假设高积分蛋白迁移率和低选择素的迁移率是迁移的固有特征，并且与潜在的细胞骨架结构相关。