MD/DPD Multiscale Framework for Predicting Morphology and Stresses of Red Blood Cells in Health and Disease

Chang, Hung-Yu; Li, Xuejin; Li, He; Karniadakis, George Em; McCulloch, Andrew D.

doi:10.1371/journal.pcbi.1005173

Title: MD/DPD Multiscale Framework for Predicting Morphology and Stresses of Red Blood Cells in Health and Disease

Journal Article · Fri Oct 28 00:00:00 EDT 2016 · PLoS Computational Biology (Online)

DOI:https://doi.org/10.1371/journal.pcbi.1005173· OSTI ID:1627248

Chang, Hung-Yu ^[1]; Li, Xuejin ^[1]; Li, He ^[1]; Karniadakis, George Em ^[1]; McCulloch, Andrew D.

Brown Univ., Providence, RI (United States). Div. of Applied Mathematics

Healthy red blood cells (RBCs) have remarkable deformability, squeezing through narrow capillaries as small as 3 microns in diameter without any damage. However, in many hematological disorders the spectrin network and lipid bilayer of diseased RBCs may be significantly altered, leading to impaired functionality including loss of deformability. We employ a two-component whole-cell multiscale model to quantify the biomechanical characteristics of the healthy and diseased RBCs, including Plasmodium falciparum-infected RBCs (Pf-RBCs) and defective RBCs in hereditary disorders, such as spherocytosis and elliptocytosis. In particular, we develop a two-step multiscale framework based on coarse-grained molecular dynamics (CGMD) and dissipative particle dynamics (DPD) to predict the static and dynamic responses of RBCs subject to tensile forcing, using experimental information only on the structural defects in the lipid bilayer, cytoskeleton, and their interaction. We first employ CGMD on a small RBC patch to compute the shear modulus, bending stiffness, and network parameters, which are subsequently used as input to a whole-cell DPD model to predict the RBC shape and corresponding stress field. For Pf-RBCs at trophozoite and schizont stages, the presence of cytoadherent knobs elevates the shear response in the lipid bilayer and stiffens the RBC membrane. For RBCs in spherocytosis and elliptocytosis, the bilayer-cytoskeleton interaction is weakened, resulting in substantial increase of the tensile stress in the lipid bilayer. Furthermore, we investigate the transient behavior of stretching deformation and shape relaxation of the normal and defective RBCs. Different from the normal RBCs possessing high elasticity, our simulations reveal that the defective RBCs respond irreversibly, i.e., they lose their ability to recover the normal biconcave shape in successive loading cycles of stretching and relaxation. Our findings provide fundamental insights into the microstructure and biomechanics of RBCs, and demonstrate that the two-step multiscale framework presented here can be used effectively for in silico studies of hematological disorders based on first principles and patient-specific experimental input at the protein level.

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Research Organization:: Argonne National Lab (ANL), Lemont, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC); Innovative and Novel Computational Impact on Theory and Experiment (INCITE)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1627248

Journal Information:: PLoS Computational Biology (Online), Vol. 12, Issue 10; ISSN 1553-7358

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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