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

ABSTRACT: 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.

SUBMITTER: Chang HY

PROVIDER: S-EPMC5085038 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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

Chang Hung-Yu HY Li Xuejin X Li He H Karniadakis George Em GE

PLoS computational biology 20161028 10

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 Plasmodiu ...[more]

PMID: 27792725

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Project description:We compare the predictive capability of two mathematical models for red blood cells (RBCs) focusing on blood flow in capillaries and arterioles. Both RBC models as well as their corresponding blood flows are based on the dissipative particle dynamics (DPD) method, a coarse-grained molecular dynamics approach. The first model employs a multiscale description of the RBC (MS-RBC), with its membrane represented by hundreds or even thousands of DPD-particles connected by springs into a triangular network in combination with out-of-plane elastic bending resistance. Extra dissipation within the network accounts for membrane viscosity, while the characteristic biconcave RBC shape is achieved by imposition of constraints for constant membrane area and constant cell volume. The second model is based on a low-dimensional description (LD-RBC) constructed as a closed torus-like ring of only 10 large DPD colloidal particles. They are connected into a ring by worm-like chain (WLC) springs combined with bending resistance. The LD-RBC model can be fitted to represent the entire range of nonlinear elastic deformations as measured by optical-tweezers for healthy and for infected RBCs in malaria. MS-RBCs suspensions model the dynamics and rheology of blood flow accurately for any vessel size but this approach is computationally expensive for vessel diameters above 100?m. Surprisingly, the much more economical suspensions of LD-RBCs also capture the blood flow dynamics and rheology accurately except for small-size vessels comparable to RBC diameter. In particular, the LD-RBC suspensions are shown to properly capture the experimental data for the apparent viscosity of blood and its cell-free layer (CFL) in tube flow. Taken together, these findings suggest a hierarchical approach in modeling blood flow in the arterial tree, whereby the MS-RBC model should be employed for capillaries and arterioles below 100?m, the LD-RBC model for arterioles, and the continuum description for arteries.

Dataset Information

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

Publications

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

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