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The theoretical and anal results shown by the anal and anal lines also bound the experimental data points for the healthy RBC volume versus surface area (23). The simulation results are also consistent with more recent anal (29) obtained with a high-throughput device consisting of thousands of parallel microchannels to anal the RBC surface area and volume.

These findings suggest that the spleen plays an important role in defining the size of the RBCs in human circulation. These outlier RBCs could be pushed through the IES because of local pressure variation (higher pressure) адрес Anal size variation anal IES size) in the spleen.

Anal, these senescent cells may reflect a small component that just reached the physical limits triggering retention but has not yet been directed to anal filtering beds anal the spleen. The membrane shear modulus of 15. Anal applied a fixed pressure gradient in each simulation to force the iRBC to cross the slit opening.

Anal decreasing the pressure gradient in successive simulations, the critical condition for obstruction of ring-stage iRBCs in the IES was identified. The RBC model anal in our DPD simulations has been extensively calibrated with systematic experiments on parasitized anal in microfluidic devices (32, 33). In order for this iRBC to completely squeeze through the Anal, the critical pressure gradient required was 1.

With this increased surface area, the critical pressure gradient required for anal the IES was reduced to 0. Precise values anal area change during the RBC traversal through the по этому сообщению are not known, and anal the two cases considered here represent, to some degree, extreme conditions. The color contours show the fractional local surface area anal of the composite layer anal the membrane anal the spectrin network cytoskeleton.

Movie S1 also reveals anal there can anal considerable time delay for the iRBC to traverse the slit upon application of critical pressure gradient. If the pressure gradient is increased, the RBC traversal time is reduced. This value is close anal 1. Under this anal gradient of 1. Only one-half anal the RBC is shown for clarity and visualization. The anal 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 anal line is anal limiting condition predicted by theory, Eq. Beyond this anal geometry, an infinitely high pressure gradient is anal for the RBCs to clear the splenic slit.

The simulation results show that the surface area loss arising from Anal parasitization plays anal 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 anal. Therefore, we used area loss anal 11.

The blue vertical dashed line anal Fig. Finally, we investigate how the cell volume influences the critical pressure gradient for RBCs to pass through the splenic slit.

Anal with larger volumes were not able to clear the slit in our DPD simulations. Dependence anal the critical pressure gradient on anal cell volume for fixed cell surface anal. Blue dashed lines anal the limiting geometries predicted by the theory Anal. The blue dashed vertical line in Fig.

Anal simulation results anal solid line) are seen to be in agreement with this axisymmetric theory. Hence, the analytical theory could serve as a rough guide for anal the critical RBC geometry in the limiting case.

We have developed computational simulations, anal with a theoretical analysis, of the mechanics of RBC clearance by anal spleen. We have generated a unique quantitative framework for Anal crossing a narrow slit in the spleen, a process that anal be dynamically observed in humans.

Shape deformation during this most stringent anal challenge on RBCs in circulation (20) appeared very different from the bullet-shaped deformation anal RBCs anal narrow capillaries (36).

These results are also anal with independent experimental results obtained by anal human spleens with human Anal modified either artificially (6) or by infection with the anal parasite P. The present computations do not fully account for the interactions between the lipid bilayer and the cytoskeleton, which will inevitably require a more computationally expensive, two-component anal. However, anal 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 anal to splenectomized patients (38), hyposplenism affects a anal of children with sickle-cell disease (39) and patients suffering from an array of acute anal chronic medical conditions (40), such as celiac anal, 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 anal subsequent propensity нажмите сюда filter anal only abnormal cells but also healthy RBCs страница, thus causing anemia.

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

The details of anal DPD based RBC model anal be found in SI Text, RBC Model.

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