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Review Article

Computational Biomechanics of Human Red Blood Cells in Hematological Disorders

[+] Author and Article Information
Xuejin Li

Division of Applied Mathematics,
Brown University,
Providence, RI 02912
e-mail: Xuejin_Li@brown.edu

He Li, Hung-Yu Chang

Division of Applied Mathematics,
Brown University,
Providence, RI 02912

George Lykotrafitis

Department of Mechanical Engineering,
University of Connecticut,
Storrs, CT 06269;
Department of Biomedical Engineering,
University of Connecticut,
Storrs, CT 06269

George Em Karniadakis

Fellow ASME
Division of Applied Mathematics,
Brown University,
Providence, RI 02912
e-mail: George_Karniadakis@brown.edu

1Corresponding authors.

Manuscript received June 30, 2016; final manuscript received October 29, 2016; published online January 19, 2017. Assoc. Editor: Victor H. Barocas.

J Biomech Eng 139(2), 020804 (Jan 19, 2017) (13 pages) Paper No: BIO-16-1277; doi: 10.1115/1.4035120 History: Received June 30, 2016; Revised October 29, 2016

We review recent advances in multiscale modeling of the biomechanical characteristics of red blood cells (RBCs) in hematological diseases, and their relevance to the structure and dynamics of defective RBCs. We highlight examples of successful simulations of blood disorders including malaria and other hereditary disorders, such as sickle-cell anemia, spherocytosis, and elliptocytosis.

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Figures

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Fig. 1

(a and b) Schematic representation of a healthy human RBC (a) and its complex membrane structure (b). The cell membrane is made of a lipid bilayer reinforced on its inner face by a flexible two-dimensional spectrin network. (c and d) Schematic view of the particle-based whole-cell model (c) and composite membrane model (d). For the whole-cell model (c), the lipid bilayer and cytoskeleton are rendered in dark gray and black triangular networks. For the coarse-grained composite membrane model (d), the dark gray, black, and light gray particles represent clusters of lipid molecules, actin junctions, and spectrin filaments of cytoskeleton, respectively; the black particles signify band-3 complexes.

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Fig. 2

Shape transformation pathways of membrane vesicles (a) and RBCs (b) obtained from experimental investigations (upper) and model predictions (lower). Reproduced from Refs. [47,105].

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Fig. 3

(a–c) Snapshot of a vesicle undergoing blebbing as a result of a localized ablation of the RBC cytoskeleton. (d–f) Sequences of coalescence of two blebs on vesicle during a uniform contraction of RBC cytoskeleton (Reproduced from Ref. [128]). CGMD modeling of one-component (g–i) and two-component (j–l) RBC membrane under uniform compression at compression ratio of (g) 2%, (h) 5%, and (i) 15%. Gray color highlights the lipid bilayer component with spontaneous curvature. The compression ratio is defined as the ratio of the decrease in the horizontally projected area due to compression, to the projected area of the membrane at equilibrium (Reproduced with permission from Li and Lykotrafitis [130]. Copyright 2015 by American Physical Society.

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Fig. 4

(a) Illustration of the flow cytometer device. (b) Experimental images of ring-stage infected (dark gray arrows) and uninfected (light gray arrows) RBCs in the channels. (c) The computational RBC model consists of 5000 particles connected with links. The parasite is modeled as a rigid sphere inside the cell. (d) DPD simulation images of Pf-RBCs traveling in channels of converging (left) and diverging (right) pore geometries. (Reproduced with permission from Bow et al. [142]. Copyright 2011 by Royal Society of Chemistry).

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Fig. 5

The twisted structure of HbS fiber (a) and its pitch length s (b) and persistence length lp (c) properties obtained from CGMD simulations. (Reproduced with permission from Lu et al. [150]. Copyright 2016 by Elsevier).

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Fig. 6

Sickle cells in shear flow: (a) Successive snapshots of SS-RBCs in shear flow. Labels I, II, and III correspond to a deformable SS2 cell, rigid SS3 cell, and ISC, respectively. The arrow indicates the flow direction; (b-c) Instantaneous contact area and velocity for sickle RBC in shear flow conditions. (Reproduced from Ref. [95]).

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Fig. 7

MSDs of band-3 particles against time and corresponding diffusion coefficients of the mobile band-3 in the membrane with various vertical (a) and horizontal (b) connectivities. (Reproduced from Ref. [98].).

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