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Mechanics of diseased red blood cells in human spleen and consequences for hereditary blood disorders

Author(s)
Li, He; Lu, Lu; Li, Xuejin; Buffet, Pierre A.; Dao, Ming; Karniadakis, George E.; Suresh, Subra; ... Show more Show less
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Abstract
In red blood cell (RBC) diseases, the spleen contributes to anemia by clearing the damaged RBCs, but its unique ability to mechanically challenge RBCs also poses the risk of inducing other pathogenic effects. We have analyzed RBCs in hereditary spherocytosis (HS) and hereditary elliptocytosis (HE), two typical examples of blood disorders that result in membrane protein defects in RBCs. We use a two-component protein-scale RBC model to simulate the traversal of the interendothelial slit (IES) in the human spleen, a stringent biomechanical challenge on healthy and diseased RBCs that cannot be directly observed in vivo. In HS, our results confirm that the RBC loses surface due to weakened cohesion between the lipid bilayer and the cytoskeleton and reveal that surface loss may result from vesiculation of the RBC as it crosses IES. In HE, traversing IES induces sustained elongation of the RBC with impaired elasticity and fragmentation in severe disease. Our simulations thus suggest that in inherited RBC disorders, the spleen not only filters out pathological RBCs but also directly contributes to RBC alterations. These results provide a mechanistic rationale for different clinical outcomes documented following splenectomy in HS patients with spectrin-deficient and ankyrin-deficient RBCs and offer insights into the pathogenic role of human spleen in RBC diseases. Keywords: spleen, hereditary spherocytosis, hereditary elliptocytosis, vesiculation, cell fragmentation
Date issued
2018-09
URI
https://hdl.handle.net/1721.1/125836
Department
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Li, He, Lu Lu, Xuejin Li et al. "Mechanics of diseased red blood cells in human spleen and consequences for hereditary blood disorders" PNAS, 115,38 (September 2018):9574-9579. Copyright © 2018 the Author(s).
Version: Final published version
ISSN
0027-8424
1091-6490

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