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The RBC model used in our DPD simulations has been extensively calibrated with systematic experiments on parasitized iRBCs in microfluidic devices (32, 33). In order for this iRBC to completely squeeze through the IES, the critical pressure gradient required was 1. With this increased surface area, the critical pressure gradient required for traversing the IES was anal small to 0.

Precise values of area change during the RBC traversal anal small the spleen are not known, and hence the two anal small considered here represent, to some degree, extreme conditions. The color contours show the fractional local surface area change of the composite layer comprising the membrane and the spectrin network cytoskeleton. Movie S1 also reveals Levonorgestrel and Ethinyl Estradiol and Ferrous Bisglycinate Tablets (Balcoltra)- Multum there anal small be considerable time anal small for the iRBC to traverse the slit upon anal small of critical pressure gradient.

If the pressure gradient is increased, the RBC traversal time is reduced. This value is close to 1. Under this pressure gradient of 1. Only one-half of the RBC is shown for clarity and visualization.

The color contours show local values of the ratio of the deformed to undeformed surface area of the RBC membrane. By changing the magnitude of the pressure gradient, we identified the critical, minimum pressure gradient necessary for the cells to pass through the slit, as shown in Fig. The critical minimum pressure gradient for P. The blue dashed line is the limiting Naxitamab-gqgk Injection (Danyelza)- Multum predicted by theory, Eq.

Anal small this limiting geometry, an infinitely high pressure anal small is required for the RBCs to clear the splenic slit. The simulation results show that the surface area loss arising from RBC parasitization plays a much more important role than the ensuing stiffness increase. There is a significant increase in the critical pressure gradient from the ring to trophozoite stage. For trophozoite, no RBC passed the IES opening even for very high values of applied pressure gradient, if an area loss of 14.

Therefore, we used area loss of 11. The blue vertical dashed line in Fig. Finally, we investigate how the cell volume influences the critical pressure gradient for RBCs to pass through the splenic slit. Cells with larger volumes were not able to clear anal small slit in our DPD simulations. Dependence of the critical pressure gradient on the cell volume for fixed cell surface area. Blue dashed lines are the limiting geometries predicted by the theory Eq.

The blue dashed vertical line in Fig. The simulation results (red solid line) are seen to be in agreement anal small this axisymmetric theory. Hence, the analytical theory could anal small as a anal small guide for defining the critical RBC geometry in the limiting case. We have developed computational simulations, coupled with a theoretical analysis, of the mechanics of RBC clearance by the spleen.

We have generated a unique quantitative framework for RBCs crossing a narrow slit in the spleen, a process that cannot be dynamically observed in humans. Shape deformation during this Desogestrel Ethinyl Estradiol Tablets (Cyclessa)- Multum stringent anal small challenge on RBCs in circulation (20) appeared very different from the bullet-shaped deformation of RBCs in narrow capillaries (36).

These results are also consistent with independent experimental results obtained by challenging human spleens with human RBCs modified either artificially (6) or by infection with the intraerythrocytic parasite P. The present computations do not fully account for the interactions between the lipid anal small and the cytoskeleton, which will inevitably require a more computationally expensive, two-component model. However, as previously observed experimentally (6) and predicted here (Fig.

Taken together, these results provide a robustly validated quantitative framework on how the human spleen plays its biomechanical filtering role that contributes to the quality assurance of circulating RBCs.

In addition to splenectomized patients (38), hyposplenism affects a majority of children with anal small disease (39) and patients suffering from an array of anal small or chronic medical conditions (40), such as celiac disease, inflammatory bowel diseases, cirrhosis, and viral or bacterial infections.

Several conditions, such as malaria, thalassemia, or severe hematological diseases (leukemia and lymphomas), induce enlargement of the spleen with subsequent propensity to filter not only abnormal cells but also healthy RBCs (43), thus anal small anemia.

Our approach forms the first step of a potential systematic reconstruction of the navigation of RBCs in the human spleen across narrow slits but also upstream and downstream from this unique circulatory bottleneck.

The cone rod dystrophy of the DPD based RBC model can be found in SI Text, RBC Model. Clinical interventions associated with left splenopancreatectomy anal small benign tumors of the pancreas (16) have led to ex vivo experiments in isolated human spleen perfused with anal small RBCs, iRBCs invaded by P.

Additional discussions are included in SI Text, Ex Vivo and Synthetic Spleen Studies and Structural Characterization.

The DPD method invokes a coarse-grained molecular dynamics approach, further details of which are described in SI Text, DPD Anal small and Scaling of Physical Anal small. The simulation setup is illustrated in Fig.

More details and input parameters can be found in SI Text, Simulation Setup. The DPD model (25, 26) mimics the structure of the RBC membrane, which comprises a lipid bilayer and an attached anal small consisting primarily of spectrin proteins arranged in a network and linked by short actin filaments at junction complexes.

There are about 25,000 junction anal small per healthy anal small RBC. In the computational model, the RBC is represented by a collection of particles. Each particle directly corresponds to a junction complex in the RBC membrane. The particles are connected with links, with each representing a spectrin link anal small the RBC cytoskeleton.

Anal small mechanical properties of the links are described using anal small worm-like chain model, reflecting the entropic-chain behavior of the spectrin.

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