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Collaborative Research: Multi-Scale Models and Quantitative Experiments of Red Blood Cells Transmigration through Inter-Endothelial Slits in the Spleen

合作研究：红细胞通过脾脏内皮间缝隙迁移的多尺度模型和定量实验

基本信息

批准号：
1948347
负责人：
Zhangli Peng
金额：
$ 10.05万
依托单位：
University of Illinois at Chicago
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-15 至 2021-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1948347&HistoricalAwards=false
关键词：
Collaborative Research Multi Scale Models

项目摘要

CBET - 1706436/1706571PIs: Peng, Zhangli/del Alamo, Juan CarlosDuring their circulation through the spleen, red blood cells are challenged to squeeze through narrow slits between endothelial cells that are much smaller than the red blood cell itself. The squeezing motion leads to large red cell deformations and significant mechanical forces on the cells that can cause cell rupture. Aged or otherwise altered red blood cells become trapped and are removed from the circulation. The goal of this collaborative project is to understand the mechanics of red blood cell transmigration through narrow slits by a combination of experiments and high-fidelity numerical modeling. Microfluidic-based experiments will be used to measure the forces required for healthy and diseased red blood cells to move through slits with well-defined widths and geometries. A multi-scale computational model will be developed to fully characterize red blood cell transmigration through slits in the spleen. The results will show how transmigration depends on the geometrical and mechanical properties of the red blood cell and its environment from the molecular level to tissue level. This research may also contribute to knowledge about other important physiological processes, including inflammation and the metastatic spread of tumors, in which transmigration of cells through narrow slits plays an important role. Elements of this project will be adapted for hands-on demonstrations for high school students, and to excite youngsters and their parents about the importance and behavior of multi-component vesicles.Squeezing through narrow gaps requires significant mechanical forces and red blood cell deformations, which can lead to bilayer-cytoskeletal detachment, cell volume change, and cell rupture. Despite the importance of transmigration to red cell maintenance, there are no quantitative data available on the deformation and stress distributions of transmigrating red blood cells. A multiscale model of red blood cell transmigration will be developed that accounts explicitly for the lipid bilayer of the cell and its underlying cytoskeleton. A force microscopy technique will be used to measure the mechanical forces experienced by red blood cells while passing through slits of controlled size, stiffness and adhesiveness. Red blood cell deformation will be visualized as they pass through the slits, and the roles of microstructural components of the cells will be examined by pharmacological manipulations. Results from the experiments will be used to validate the computational model. The model in combination with experiment will be used to investigate how molecular alterations affect the filtration of RBCs in the spleen when the microstructural organization of the cells and the splenic environment are systematically altered. Results from these studies will be useful in understanding cellular deformation in physiological processes and in biomedical devices where cells undergo large deformations.

CBET - 1706436/1706571 PI：Peng，Zhangli/del Alamo，Juan Carlos在通过脾脏的循环过程中，红细胞受到挑战，通过比红细胞本身小得多的内皮细胞之间的狭窄缝隙挤压。挤压运动导致大的红细胞变形和细胞上的显著机械力，其可导致细胞破裂。老化或以其他方式改变的红细胞被捕获并从循环中移除。该合作项目的目标是通过实验和高保真数值模拟相结合来了解红细胞通过窄缝迁移的机制。基于微流体的实验将用于测量健康和患病红细胞通过具有明确定义的宽度和几何形状的狭缝所需的力。将开发一个多尺度计算模型，以充分表征红细胞通过脾脏狭缝的迁移。结果将显示，从分子水平到组织水平，红细胞及其环境的几何和机械特性如何决定轮回。这项研究也可能有助于了解其他重要的生理过程，包括炎症和肿瘤的转移性扩散，其中细胞通过狭缝的迁移起着重要作用。该项目的内容将适用于高中生的实践演示，并激发年轻人和他们的父母对多组分囊泡的重要性和行为的兴趣。通过狭窄的间隙挤压需要显著的机械力和红细胞变形，这可能导致双层细胞骨架分离，细胞体积变化和细胞破裂。尽管红细胞维持的重要性，有没有定量数据的变形和应力分布的红细胞迁移。将开发红细胞迁移的多尺度模型，明确解释细胞的脂双层及其底层细胞骨架。力显微镜技术将用于测量红细胞在通过受控尺寸、刚度和刚度的狭缝时所经受的机械力。红细胞变形将在它们通过狭缝时可视化，并且细胞的微观结构组分的作用将通过药理学操作来检查。实验结果将用于验证计算模型。结合实验的模型将用于研究当细胞的微观结构组织和脾环境系统地改变时，分子改变如何影响脾中RBC的过滤。这些研究的结果将有助于了解细胞变形的生理过程和生物医学设备中的细胞经历大的变形。