Exploring mechanisms of aquaporin-mediated cell migration

项目摘要 PI的实验室探索机械力在生理和病理现象中的作用。完成 为了实现这一目标，他们使用生物工程工具设计和探测多尺度生物系统的体外模型 如微加工设备;细胞、分子生物学技术和细胞力学的新组合 工具和定制定量图像处理软件。他们目前在三个主要实验室中使用该框架 重点领域：（1）在健康，疾病， （2）探测健康和疾病中血脑屏障（BBB）处的细胞-细胞相互作用;以及 (3)使用工程细胞技术理解细胞粘附、迁移和分裂的基本机制 微环境和模型细胞系统。在接下来的5年里，PI的目标是建立一个NIGMS-MIRA， 一项由基金资助的研究计划，旨在探索关键的、悬而未决的问题，即水通道蛋白（ 细胞膜）调节细胞迁移。 PI提出的MIRA研究计划的动机是强有力的现象学证据， 水通道蛋白（AQP）在细胞迁移中的作用，加上AQP表达或功能之间缺乏机制联系， 和细胞行为，这就留下了关于AQP如何促进这些生理性的关键问题。 现象。因此，拟议的工作旨在探讨与基本方面有关的许多问题 关于细胞迁移的调节，问题集中在AQP是否以及如何调节细胞迁移。 极化、细胞生物力学性质、迁移表型和对微环境的反应。的 PI的实验室具有独特的优势，可以使用集成的实验和 理论方法，通过结合我们在细胞迁移，细胞机械生物学和 生物力学、活细胞成像、分子生物学、微加工和微环境工程，以及 定量分析相

PROJECT SUMMARY The PI’s lab explores the role of mechanical forces in physiological and pathological phenomena. To accomplish this goal, they engineer and probe in vitro models of multi-scale biological systems using bioengineering tools such as microfabricated devices; novel combinations of cells, molecular biology techniques, and cell mechanics tools; and custom quantitative image processing software. They currently use this framework in three main lab focus areas: (1) Exploring the mechanobiology of the vascular endothelium in the context of health, disease, and drug delivery; (2) Probing cell-cell interactions at the blood-brain barrier (BBB) in health and disease; and (3) Understanding basic mechanisms of cell adhesion, migration, and division using engineered cellular microenvironments and model cell systems. Over the next 5 years, the PI’s goal is to establish an NIGMS-MIRA- funded research program that explores critical, outstanding questions about how aquaporins (water channels on the cell membrane) regulate cell migration. The PI’s proposed MIRA research program is motivated by strong phenomonological evidence for the role of aquaporins (AQPs) in cell migration, coupled with a lack of mechanistic links between AQP expression or function and cell behavior, which leaves open critical questions about how AQPs contribute to these physiological phenomena. Hence, the proposed work seeks to explore numerous questions related to fundamental aspects about the regulation of cell migration, with questions centering around whether and how AQPs modulate cell polarization, cell biomechanical properties, migration phenotypes, and response to the microenvironment. The PI’s lab is uniquely positioned to address these outstanding questions using an integrated experimental and theoretical approach, by incorporating our established techniques in cell migration, cell mechanobiology and biomechanics, live cell imaging, molecular biology, microfabrication and microenvironment engineering, and quantitative analysis.