skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Mesoscopic Adaptive Resolution Scheme toward Understanding of Interactions between Sickle Cell Fibers

Abstract

Understanding of intracellular polymerization of sickle hemoglobin (HbS) and subsequent interaction with the membrane of a red blood cell (RBC) is important to predict the altered morphologies and mechanical properties of sickle RBCs in sickle cell anemia. However, modeling the integrated processes of HbS nucleation, polymerization, HbS fiber interaction, and subsequent distortion of RBCs is challenging as they occur at multispatial scales, ranging from nanometers to micrometers. To make progress toward simulating the integrated processes, we propose a hybrid HbS fiber model, which couples fine-grained and coarse-grained HbS fiber models through a mesoscopic adaptive resolution scheme (MARS). To this end, we apply a microscopic model to capture the dynamic process of polymerization of HbS fibers, while maintaining the mechanical properties of polymerized HbS fibers by the mesoscopic model, thus providing a means of bridging the subcellular and cellular phenomena in sickle cell disease. At the subcellular level, this model can simulate HbS polymerization with preexisting HbS nuclei. At the cellular level, if combined with RBC models, the generated HbS fibers could be applied to study the morphologies and membrane stiffening of sickle RBCs. One important feature of the MARS is that it can be easily employed in other particle-based multiscalemore » simulations where a dynamic coarse-graining and force-blending method is required. As demonstrations, we first apply the hybrid HbS fiber model to simulate the interactions of two growing fibers and find that their final configurations depend on the orientation and interaction distance between two fibers, in good agreement with experimental observations. We also model the formation of fiber bundles and domains so that we explore the mechanism that causes fiber branching.« less

Authors:
; ; ; ;
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Oak Ridge Leadership Computing Facility (OLCF)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1565552
DOE Contract Number:  
AC02-06CH11357; AC05-00OR22725
Resource Type:
Journal Article
Journal Name:
Biophysical Journal
Additional Journal Information:
Journal Volume: 113; Journal Issue: 1; Journal ID: ISSN 0006-3495
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
Biophysics

Citation Formats

Lu, Lu, Li, He, Bian, Xin, Li, Xuejin, and Karniadakis, George Em. Mesoscopic Adaptive Resolution Scheme toward Understanding of Interactions between Sickle Cell Fibers. United States: N. p., 2017. Web. doi:10.1016/j.bpj.2017.05.050.
Lu, Lu, Li, He, Bian, Xin, Li, Xuejin, & Karniadakis, George Em. Mesoscopic Adaptive Resolution Scheme toward Understanding of Interactions between Sickle Cell Fibers. United States. doi:10.1016/j.bpj.2017.05.050.
Lu, Lu, Li, He, Bian, Xin, Li, Xuejin, and Karniadakis, George Em. Sat . "Mesoscopic Adaptive Resolution Scheme toward Understanding of Interactions between Sickle Cell Fibers". United States. doi:10.1016/j.bpj.2017.05.050.
@article{osti_1565552,
title = {Mesoscopic Adaptive Resolution Scheme toward Understanding of Interactions between Sickle Cell Fibers},
author = {Lu, Lu and Li, He and Bian, Xin and Li, Xuejin and Karniadakis, George Em},
abstractNote = {Understanding of intracellular polymerization of sickle hemoglobin (HbS) and subsequent interaction with the membrane of a red blood cell (RBC) is important to predict the altered morphologies and mechanical properties of sickle RBCs in sickle cell anemia. However, modeling the integrated processes of HbS nucleation, polymerization, HbS fiber interaction, and subsequent distortion of RBCs is challenging as they occur at multispatial scales, ranging from nanometers to micrometers. To make progress toward simulating the integrated processes, we propose a hybrid HbS fiber model, which couples fine-grained and coarse-grained HbS fiber models through a mesoscopic adaptive resolution scheme (MARS). To this end, we apply a microscopic model to capture the dynamic process of polymerization of HbS fibers, while maintaining the mechanical properties of polymerized HbS fibers by the mesoscopic model, thus providing a means of bridging the subcellular and cellular phenomena in sickle cell disease. At the subcellular level, this model can simulate HbS polymerization with preexisting HbS nuclei. At the cellular level, if combined with RBC models, the generated HbS fibers could be applied to study the morphologies and membrane stiffening of sickle RBCs. One important feature of the MARS is that it can be easily employed in other particle-based multiscale simulations where a dynamic coarse-graining and force-blending method is required. As demonstrations, we first apply the hybrid HbS fiber model to simulate the interactions of two growing fibers and find that their final configurations depend on the orientation and interaction distance between two fibers, in good agreement with experimental observations. We also model the formation of fiber bundles and domains so that we explore the mechanism that causes fiber branching.},
doi = {10.1016/j.bpj.2017.05.050},
journal = {Biophysical Journal},
issn = {0006-3495},
number = 1,
volume = 113,
place = {United States},
year = {2017},
month = {7}
}