Multiscale Modeling of Splenic Filtrations of Healthy and Diseased Red Blood Cells

We apply multiscale modeling to investigate the mechanical filtrations of healthy and diseased red blood cells (RBCs) through inter-endothelial slits in the spleen. Our results show that the spleen plays an important role in determining distributions of size and shape of healthy RBCs in the circulation. The predicted cell deformation and velocity are validated against microfluidic experiments. The detailed cytoskeletal shear deformation, bilayer tension, and bilayer-cytoskeletal interaction stresses are predicted as functions of hydrodynamic pressure, shear modulus, and geometries of cells and slits. Furthermore, we investigate how single point mutations of cytoskeletal spectrins affect the splenic filtration of RBCs by bridging molecular dynamics, coarse graining, and finite elements. Our preliminary results show that due to point mutations, the distortion of the linker helix of spectrins in hereditary elliptocytosis (HE) would change the force-length curves of spectrin tetramers and the free energy surfaces of spectrin networks. We found that the altered mechanical properties of RBC membranes in HE could increase the probability of vesiculations during splenic filtration.