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

Thomas G. Fai, Alejandra Leo-Macias, David L. Stokes, Charles Peskin

Research output: Contribution to journalArticle

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 protect against failure in the case of a red cell subjected to an applied strain. The methods presented here could form the basis of disease- and patient-specific computational studies of hereditary diseases affecting the red cell cytoskeleton.

Original languageEnglish (US)
Article numbere1005790
JournalPLoS Computational Biology
Volume13
Issue number10
DOIs
StatePublished - Oct 1 2017

Fingerprint

spectrin
Cytoskeleton
Spectrin
Red Blood Cells
cytoskeleton
Blood
erythrocytes
Erythrocytes
blood
Cells
Lipid bilayers
simulation
Immersed Boundary Method
Lipid Bilayer
lipid bilayers
Simulation
Lipid Bilayers
Resist
shear stress
lipid

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Ecology
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics

Cite this

Image-based model of the spectrin cytoskeleton for red blood cell simulation. / Fai, Thomas G.; Leo-Macias, Alejandra; Stokes, David L.; Peskin, Charles.

In: PLoS Computational Biology, Vol. 13, No. 10, e1005790, 01.10.2017.

Research output: Contribution to journalArticle

Fai, Thomas G. ; Leo-Macias, Alejandra ; Stokes, David L. ; Peskin, Charles. / Image-based model of the spectrin cytoskeleton for red blood cell simulation. In: PLoS Computational Biology. 2017 ; Vol. 13, No. 10.
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