Exploring mechanisms of aquaporin-mediated cell migration

项目总结 PI的实验室探索了机械力在生理和病理现象中的作用。要完成 为了达到这个目标，他们利用生物工程工具设计和探索了多尺度生物系统的体外模型。 例如微型制造设备；细胞、分子生物学技术和细胞力学的新组合 工具；以及定制的定量图像处理软件。他们目前在三个主要实验中使用此框架 重点领域：(1)在健康、疾病、 和药物输送；(2)探测健康和疾病中血脑屏障(BBB)的细胞-细胞相互作用；以及 (3)利用工程细胞了解细胞黏附、迁移和分裂的基本机制 微环境和模型细胞系统。在未来5年，PI的目标是建立NIGMS-MIRA- 受资助的研究项目，探索有关水通道蛋白(水通道如何在 细胞膜)调节细胞迁移。 PI提出的Mira研究计划是由强有力的现象学证据推动的 水通道蛋白(AQP)在细胞迁移中的作用，以及AQP表达或功能之间缺乏机制联系 以及细胞行为，这留下了一些关键的问题，即水通道蛋白是如何促进这些生理的 现象。因此，拟议的工作试图探讨与基本方面有关的许多问题。 关于细胞迁移的调节，问题集中在水通道蛋白是否以及如何调节细胞 极化、细胞生物力学特性、迁移表型和对微环境的响应。这个 PI的实验室独特地定位于解决这些悬而未决的问题，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、微制造和微环境工程 定量分析。

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.