CBET - 1706436/1706571 PIs: Peng, Zhangli/del Alamo, Juan Carlos
During 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.