Please use this identifier to cite or link to this item:
Title: Mechanics of diseased red blood cells in human spleen and consequences for hereditary blood disorders
Authors: Li, He
Lu, Lu
Li, Xuejin
Buffet, Pierre A.
Dao, Ming
Karniadakis, George E.
Suresh, Subra
Keywords: Engineering::Materials
Hereditary Spherocytosis
Issue Date: 2018
Source: Li, H., Lu, L., Li, X., Buffet, P. A., Dao, M., Karniadakis, G. E., & Suresh, S. (2018). Mechanics of diseased red blood cells in human spleen and consequences for hereditary blood disorders. Proceedings of the National Academy of Sciences, 115(38), 9574-9579. doi:10.1073/pnas.1806501115
Series/Report no.: Proceedings of the National Academy of Sciences
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.
ISSN: 0027-8424
DOI: 10.1073/pnas.1806501115
Rights: © 2018 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:MSE Journal Articles

Citations 10

Updated on Mar 10, 2021

Citations 10

Updated on Mar 10, 2021

Page view(s)

Updated on Jun 23, 2022

Download(s) 50

Updated on Jun 23, 2022

Google ScholarTM




Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.