Exploring mechanisms of aquaporin-mediated cell migration

探索水通道蛋白介导的细胞迁移机制

基本信息

批准号：
10810252
负责人：
Kimberly Stroka
金额：
$ 1.08万
依托单位：
UNIV OF MARYLAND, COLLEGE PARK
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10810252
关键词：
Address Area Biomechanics Biomedical Engineering Blood - brain barrier anatomy Cell Adhesion Cell Communication Cell Volumes Cell membrane Cell model Cell surface Cells Computer software Coupled Custom Disease Drug Delivery Systems Engineering Funding Goals Health Human Development Immune response Integral Membrane Protein Link Location Mechanics Mediating Microfabrication Molecular Biology Molecular Biology Techniques National Institute of General Medical Sciences Neoplasm Metastasis Pathologic Phenotype Physiological Positioning Attribute Process Property Regulation Research Role Signal Transduction System Techniques Vascular Endothelium Work biological systems cell behavior cell motility cellular engineering fascinate image processing in vitro Model live cell imaging mechanical force microdevice migration multi-scale modeling novel polarized cell programs quantitative imaging response tool water channel wound healing

项目摘要

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.

项目摘要 PI实验室探讨了机械力在物理和病理现象中的作用。完成他们的目标是使用生物工程工具来设计多尺度生物系统的体外模型例如微制设备；细胞，分子生物学技术和细胞力学的新型组合工具;和自定义定量图像处理软件。他们目前在三个主实验室中使用此框架焦点区域：（1）在健康，疾病，探索血管内皮的机制和药物输送；（2）在健康和疾病中探测血脑屏障（BBB）的细胞细胞相互作用；和（3）使用工程细胞了解细胞粘附，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年中，PI的目标是建立一个Nigms-Mira- 资助的研究计划，探讨了有关水通道蛋白的关键，悬而未决的问题（水通道开启细胞膜）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激励的细胞迁移中的水通道蛋白（AQP），再加上AQP表达式或功能之间缺乏机械联系和细胞行为，这留下了有关AQP如何贡献这些生理的关键问题现象。因此，拟议的工作旨在探索许多与基本方面有关的问题关于细胞迁移的调节，围绕AQP是否调制细胞的问题。极化，细胞生物力学特性，迁移表型以及对微环境的反应。 Pi的实验室的独特位置可以使用集成的实验和理论方法，通过编码我们在细胞迁移，细胞机制和生物力学，活细胞成像，分子生物学，微观生物和微环境工程以及定量分析。