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

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),...

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Main Authors: Li, He, Lu, Lu, Li, Xuejin, Buffet, Pierre A., Dao, Ming, Karniadakis, George E., Suresh, Subra
Other Authors: School of Materials Science & Engineering
Format: Article
Language:English
Published: 2019
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Online Access:https://hdl.handle.net/10356/83299
http://hdl.handle.net/10220/50097
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-832992023-07-14T15:45:37Z Mechanics of diseased red blood cells in human spleen and consequences for hereditary blood disorders Li, He Lu, Lu Li, Xuejin Buffet, Pierre A. Dao, Ming Karniadakis, George E. Suresh, Subra School of Materials Science & Engineering Engineering::Materials Spleen Hereditary Spherocytosis 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. Published version 2019-10-08T03:41:50Z 2019-12-06T15:19:32Z 2019-10-08T03:41:50Z 2019-12-06T15:19:32Z 2018 Journal Article 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 0027-8424 https://hdl.handle.net/10356/83299 http://hdl.handle.net/10220/50097 10.1073/pnas.1806501115 en Proceedings of the National Academy of Sciences © 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). 6 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Engineering::Materials
Spleen
Hereditary Spherocytosis
spellingShingle Engineering::Materials
Spleen
Hereditary Spherocytosis
Li, He
Lu, Lu
Li, Xuejin
Buffet, Pierre A.
Dao, Ming
Karniadakis, George E.
Suresh, Subra
Mechanics of diseased red blood cells in human spleen and consequences for hereditary blood disorders
description 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.
author2 School of Materials Science & Engineering
author_facet School of Materials Science & Engineering
Li, He
Lu, Lu
Li, Xuejin
Buffet, Pierre A.
Dao, Ming
Karniadakis, George E.
Suresh, Subra
format Article
author Li, He
Lu, Lu
Li, Xuejin
Buffet, Pierre A.
Dao, Ming
Karniadakis, George E.
Suresh, Subra
author_sort Li, He
title Mechanics of diseased red blood cells in human spleen and consequences for hereditary blood disorders
title_short Mechanics of diseased red blood cells in human spleen and consequences for hereditary blood disorders
title_full Mechanics of diseased red blood cells in human spleen and consequences for hereditary blood disorders
title_fullStr Mechanics of diseased red blood cells in human spleen and consequences for hereditary blood disorders
title_full_unstemmed Mechanics of diseased red blood cells in human spleen and consequences for hereditary blood disorders
title_sort mechanics of diseased red blood cells in human spleen and consequences for hereditary blood disorders
publishDate 2019
url https://hdl.handle.net/10356/83299
http://hdl.handle.net/10220/50097
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