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

[参考翻译]：彭，张莉/del Alamo， Juan carlos在通过脾脏的循环过程中，红细胞面临着挤压内皮细胞之间狭窄缝隙的挑战，而内皮细胞比红细胞本身小得多。挤压运动导致大的红细胞变形和显著的机械力在细胞上，可以导致细胞破裂。老化或其他改变的红细胞被困住并从循环中移除。这个合作项目的目标是通过实验和高保真数值模拟的结合来了解红细胞通过狭窄缝隙的迁移机制。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转运。结果将显示，从分子水平到组织水平，红细胞的几何和机械特性及其环境是如何影响转体的。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，在这些生理过程中，细胞通过窄缝的转运起着重要作用。这个项目的元素将被改编为高中生的动手演示，并让青少年和他们的父母对多组分囊泡的重要性和行为感到兴奋。挤压通过狭窄的间隙需要巨大的机械力和红细胞变形，这可能导致双层细胞骨架脱离，细胞体积变化和细胞破裂。尽管转运对红细胞的维持很重要，但目前还没有关于转运红细胞变形和应力分布的定量数据。一个红细胞迁移的多尺度模型将被开发出来，明确地说明细胞的脂质双分子层及其潜在的细胞骨架。一种力显微镜技术将用于测量红细胞在通过控制大小、硬度和黏附性的狭缝时所经历的机械力。当红细胞通过狭缝时，红细胞的变形将被可视化，细胞的微观结构成分的作用将通过药理学操作进行检查。实验结果将用于验证计算模型。该模型将与实验相结合，探讨当细胞的微观结构组织和脾脏环境发生系统性改变时，分子改变如何影响脾脏中红细胞的过滤。这些研究的结果将有助于理解生理过程中的细胞变形和生物医学设备中细胞发生大变形的情况。

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.