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

Title: Image-based model of the spectrin cytoskeleton for red blood cell simulation

Abstract

We simulate deformable red blood cells in the microcirculation using the immersed boundary method with a cytoskeletal model that incorporates structural details revealed by tomographic images. The elasticity of red blood cells is known to be supplied by both their lipid bilayer membranes, which resist bending and local changes in area, and their cytoskeletons, which resist in-plane shear. The cytoskeleton consists of spectrin tetramers that are tethered to the lipid bilayer by ankyrin and by actin-based junctional complexes. We model the cytoskeleton as a random geometric graph, with nodes corresponding to junctional complexes and with edges corresponding to spectrin tetramers such that the edge lengths are given by the end-to-end distances between nodes. The statistical properties of this graph are based on distributions gathered from three-dimensional tomographic images of the cytoskeleton by a segmentation algorithm. We show that the elastic response of our model cytoskeleton, in which the spectrin polymers are treated as entropic springs, is in good agreement with the experimentally measured shear modulus. By simulating red blood cells in flow with the immersed boundary method, we compare this discrete cytoskeletal model to an existing continuum model and predict the extent to which dynamic spectrin network connectivity can protectmore » against failure in the case of a red cell subjected to an applied strain. As a result, the methods presented here could form the basis of disease- and patient-specific computational studies of hereditary diseases affecting the red cell cytoskeleton.« less

Authors:
ORCiD logo [1]; ORCiD logo [2];  [2];  [2];  [3]
  1. Harvard Univ., Cambridge, MA (United States)
  2. New York Univ. (NYU), NY (United States)
  3. Univ. of Pennsylvania, Philadelphia, PA (United States)
Publication Date:
Research Org.:
Krell Inst., Ames, Iowa (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1499877
Grant/Contract Number:  
FG02-97ER25308
Resource Type:
Accepted Manuscript
Journal Name:
PLoS Computational Biology (Online)
Additional Journal Information:
Journal Name: PLoS Computational Biology (Online); Journal Volume: 13; Journal Issue: 10; Journal ID: ISSN 1553-7358
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Fai, Thomas G., Leo-Macias, Alejandra, Stokes, David L., Peskin, Charles S., and Diamond, Scott L. Image-based model of the spectrin cytoskeleton for red blood cell simulation. United States: N. p., 2017. Web. doi:10.1371/journal.pcbi.1005790.
Fai, Thomas G., Leo-Macias, Alejandra, Stokes, David L., Peskin, Charles S., & Diamond, Scott L. Image-based model of the spectrin cytoskeleton for red blood cell simulation. United States. doi:10.1371/journal.pcbi.1005790.
Fai, Thomas G., Leo-Macias, Alejandra, Stokes, David L., Peskin, Charles S., and Diamond, Scott L. Mon . "Image-based model of the spectrin cytoskeleton for red blood cell simulation". United States. doi:10.1371/journal.pcbi.1005790. https://www.osti.gov/servlets/purl/1499877.
@article{osti_1499877,
title = {Image-based model of the spectrin cytoskeleton for red blood cell simulation},
author = {Fai, Thomas G. and Leo-Macias, Alejandra and Stokes, David L. and Peskin, Charles S. and Diamond, Scott L.},
abstractNote = {We simulate deformable red blood cells in the microcirculation using the immersed boundary method with a cytoskeletal model that incorporates structural details revealed by tomographic images. The elasticity of red blood cells is known to be supplied by both their lipid bilayer membranes, which resist bending and local changes in area, and their cytoskeletons, which resist in-plane shear. The cytoskeleton consists of spectrin tetramers that are tethered to the lipid bilayer by ankyrin and by actin-based junctional complexes. We model the cytoskeleton as a random geometric graph, with nodes corresponding to junctional complexes and with edges corresponding to spectrin tetramers such that the edge lengths are given by the end-to-end distances between nodes. The statistical properties of this graph are based on distributions gathered from three-dimensional tomographic images of the cytoskeleton by a segmentation algorithm. We show that the elastic response of our model cytoskeleton, in which the spectrin polymers are treated as entropic springs, is in good agreement with the experimentally measured shear modulus. By simulating red blood cells in flow with the immersed boundary method, we compare this discrete cytoskeletal model to an existing continuum model and predict the extent to which dynamic spectrin network connectivity can protect against failure in the case of a red cell subjected to an applied strain. As a result, the methods presented here could form the basis of disease- and patient-specific computational studies of hereditary diseases affecting the red cell cytoskeleton.},
doi = {10.1371/journal.pcbi.1005790},
journal = {PLoS Computational Biology (Online)},
number = 10,
volume = 13,
place = {United States},
year = {2017},
month = {10}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 3 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Fluid-mechanical interaction of flexible bacterial flagella by the immersed boundary method
journal, March 2012


Mechanical Properties of the Red Cell Membrane in Relation to Molecular Structure and Genetic Defects
journal, June 1994


Simulation of Osmotic Swelling by the Stochastic Immersed Boundary Method
journal, January 2015

  • Wu, Chen-Hung; Fai, Thomas G.; Atzberger, Paul J.
  • SIAM Journal on Scientific Computing, Vol. 37, Issue 4
  • DOI: 10.1137/14098404X

Multiple stiffening effects of nanoscale knobs on human red blood cells infected with Plasmodium falciparum malaria parasite
journal, April 2015

  • Zhang, Yao; Huang, Changjin; Kim, Sangtae
  • Proceedings of the National Academy of Sciences, Vol. 112, Issue 19
  • DOI: 10.1073/pnas.1505584112

Modeling of Fibrin Gels Based on Confocal Microscopy and Light-Scattering Data
journal, March 2013


Mechanics of the human red blood cell deformed by optical tweezers
journal, November 2003

  • Dao, M.; Lim, C. T.; Suresh, S.
  • Journal of the Mechanics and Physics of Solids, Vol. 51, Issue 11-12
  • DOI: 10.1016/j.jmps.2003.09.019

Accurate Coarse-Grained Modeling of Red Blood Cells
journal, September 2008


Modeling Viscoelastic Networks and Cell Deformation in the Context of the Immersed Boundary Method
journal, November 1998


Tank-Tread Frequency of the Red Cell Membrane: Dependence on the Viscosity of the Suspending Medium
journal, October 2007


Tank-treading and tumbling frequencies of capsules and red blood cells
journal, April 2011

  • Yazdani, Alireza Z. K.; Kalluri, R. Murthy; Bagchi, Prosenjit
  • Physical Review E, Vol. 83, Issue 4
  • DOI: 10.1103/PhysRevE.83.046305

The micromechanics of three-dimensional collagen-I gels
journal, August 2010

  • Stein, Andrew M.; Vader, David A.; Weitz, David A.
  • Complexity, Vol. 16, Issue 4
  • DOI: 10.1002/cplx.20332

Quantifying the biophysical characteristics of Plasmodium-falciparum -parasitized red blood cells in microcirculation
journal, December 2010

  • Fedosov, D. A.; Caswell, B.; Suresh, S.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 1
  • DOI: 10.1073/pnas.1009492108

Coupling biochemistry and hydrodynamics captures hyperactivated sperm motility in a simple flagellar model
journal, August 2011

  • Olson, Sarah D.; Suarez, Susan S.; Fauci, Lisa J.
  • Journal of Theoretical Biology, Vol. 283, Issue 1
  • DOI: 10.1016/j.jtbi.2011.05.036

Modeling of band-3 protein diffusion in the normal and defective red blood cell membrane
journal, January 2016


The properties of polyunsaturated lecithins in monolayers and liposomes and the interactions of these lecithins with cholesterol
journal, April 1972

  • Demel, R. A.; Geurts van Kessel, W. S. M.; van Deenen, L. L. M.
  • Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 266, Issue 1
  • DOI: 10.1016/0005-2736(72)90116-2

Modeling viscoelastic networks in Stokes flow
journal, November 2014

  • Wróbel, Jacek K.; Cortez, Ricardo; Fauci, Lisa
  • Physics of Fluids, Vol. 26, Issue 11
  • DOI: 10.1063/1.4900941

Molecular maps of red cell deformation: hidden elasticity and in situ connectivity
journal, November 1994


The sensing of poorly deformable red blood cells by the human spleen can be mimicked in vitro
journal, February 2011


Properties of Discrete Delta Functions and Local Convergence of the Immersed Boundary Method
journal, January 2012

  • Liu, Yang; Mori, Yoichiro
  • SIAM Journal on Numerical Analysis, Vol. 50, Issue 6
  • DOI: 10.1137/110836699

Thermal Fluctuations of Red Blood Cell Membrane via a Constant-Area Particle-Dynamics Model
journal, October 2005


The Physiological Molecular Shape of Spectrin: A Compact Supercoil Resembling a Chinese Finger Trap
journal, June 2015


Actin, Spectrin, and Associated Proteins Form a Periodic Cytoskeletal Structure in Axons
journal, December 2012


The membrane skeleton of erythrocytes. A percolation model
journal, June 1990


A stochastic immersed boundary method for fluid-structure dynamics at microscopic length scales
journal, June 2007

  • Atzberger, Paul J.; Kramer, Peter R.; Peskin, Charles S.
  • Journal of Computational Physics, Vol. 224, Issue 2
  • DOI: 10.1016/j.jcp.2006.11.015

A computational model of ameboid deformation and locomotion
journal, August 1998

  • Bottino, Dean C.; Fauci, Lisa J.
  • European Biophysics Journal, Vol. 27, Issue 5
  • DOI: 10.1007/s002490050163

Stepwise Unfolding of Ankyrin Repeats in a Single Protein Revealed by Atomic Force Microscopy
journal, February 2006


Spectrin-Level Modeling of the Cytoskeleton and Optical Tweezers Stretching of the Erythrocyte
journal, May 2005


Novel structural labeling method using cryo-electron tomography and biotin–streptavidin system
journal, September 2013


The immersed boundary method
journal, January 2002


Native Ultrastructure of the Red Cell Cytoskeleton by Cryo-Electron Tomography
journal, November 2011


Cytoskeletal dynamics of human erythrocyte
journal, March 2007

  • Li, J.; Lykotrafitis, G.; Dao, M.
  • Proceedings of the National Academy of Sciences, Vol. 104, Issue 12
  • DOI: 10.1073/pnas.0700257104

Dysfunction in the βII Spectrin–Dependent Cytoskeleton Underlies Human Arrhythmia
journal, February 2015


Active elastic network: Cytoskeleton of the red blood cell
journal, January 2007


Lipid bilayer and cytoskeletal interactions in a red blood cell
journal, July 2013

  • Peng, Z.; Li, X.; Pivkin, I. V.
  • Proceedings of the National Academy of Sciences, Vol. 110, Issue 33
  • DOI: 10.1073/pnas.1311827110

Shear-Response of the Spectrin Dimer-Tetramer Equilibrium in the Red Blood Cell Membrane
journal, June 2002

  • An, Xiuli; Lecomte, M. Christine; Chasis, Joel Anne
  • Journal of Biological Chemistry, Vol. 277, Issue 35
  • DOI: 10.1074/jbc.M204567200

Imaging of the diffusion of single band 3 molecules on normal and mutant erythrocytes
journal, June 2009


Molecularly based analysis of deformation of spectrin network and human erythrocyte
journal, September 2006


Computer simulation of a model network for the erythrocyte cytoskeleton
journal, August 1994


Ultrastructure and immunocytochemistry of the isolated human erythrocyte membrane skeleton
journal, January 1993

  • Ursitti, Jeanine A.; Wade, James B.
  • Cell Motility and the Cytoskeleton, Vol. 25, Issue 1
  • DOI: 10.1002/cm.970250105

An algorithm for extracting the network geometry of three-dimensional collagen gels
journal, December 2008


Digital topology: Introduction and survey
journal, December 1989


Multiscale Modeling of Red Blood Cell Mechanics and Blood Flow in Malaria
journal, December 2011


Immersed Boundary Method for Variable Viscosity and Variable Density Problems Using Fast Constant-Coefficient Linear Solvers I: Numerical Method and Results
journal, January 2013

  • Fai, Thomas G.; Griffith, Boyce E.; Mori, Yoichiro
  • SIAM Journal on Scientific Computing, Vol. 35, Issue 5
  • DOI: 10.1137/120903038

Mechanics and Thermodynamics of Biomembranes
journal, November 1980

  • Evans, E. A.; Skalak, R.; Weinbaum, S.
  • Journal of Biomechanical Engineering, Vol. 102, Issue 4
  • DOI: 10.1115/1.3138234

Erythrocyte Membrane Model with Explicit Description of the Lipid Bilayer and the Spectrin Network
journal, August 2014


Flow-induced channel formation in the cytoplasm of motile cells
journal, July 2011


Stretching DNA
journal, December 1995


Elastic area compressibility modulus of red cell membrane
journal, June 1976


Influence of network topology on the elasticity of the red blood cell membrane skeleton
journal, May 1997


Forced Unfolding of Proteins Within Cells
journal, August 2007


Physically-Induced Cytoskeleton Remodeling of Cells in Three-Dimensional Culture
journal, December 2012


Mammalian  I-spectrin is a neofunctionalized polypeptide adapted to small highly deformable erythrocytes
journal, January 2006

  • Salomao, M.; An, X.; Guo, X.
  • Proceedings of the National Academy of Sciences, Vol. 103, Issue 3
  • DOI: 10.1073/pnas.0507661103

2–D Parachute Simulation by the Immersed Boundary Method
journal, January 2006


Large deformation of red blood cell ghosts in a simple shear flow
journal, August 1998

  • Eggleton, C. D.; Popel, A. S.
  • Physics of Fluids, Vol. 10, Issue 8
  • DOI: 10.1063/1.869703

Cooperativity in Forced Unfolding of Tandem Spectrin Repeats
journal, January 2003


Shape Memory of Human Red Blood Cells
journal, May 2004


Cell ageing for 1 day alters both membrane elasticity and viscosity
journal, February 2003


Self-Association of Human Spectrin. A Thermodynamic and Kinetic Study
journal, August 1978


Biomechanics of red blood cells in human spleen and consequences for physiology and disease
journal, June 2016

  • Pivkin, Igor V.; Peng, Zhangli; Karniadakis, George E.
  • Proceedings of the National Academy of Sciences, Vol. 113, Issue 28
  • DOI: 10.1073/pnas.1606751113

Single molecule force spectroscopy of spectrin repeats: low unfolding forces in helix bundles 1 1Edited by W. Baumeister
journal, February 1999

  • Rief, Matthias; Pascual, Jaime; Saraste, Matti
  • Journal of Molecular Biology, Vol. 286, Issue 2
  • DOI: 10.1006/jmbi.1998.2466

Motion of a tank-treading ellipsoidal particle in a shear flow
journal, July 1982


Hereditary spherocytosis, elliptocytosis, and other red cell membrane disorders
journal, July 2013


Simulations of the Erythrocyte Cytoskeleton at Large Deformation. II. Micropipette Aspiration
journal, September 1998