Deformation behaviour of stomatocyte, discocyte and echinocyte red blood cell morphologies during optical tweezers stretching

N. M. Geekiyanage, E. Sauret, S. C. Saha, R. L. Flower & Y. T. Gu

The red blood cell (RBC) deformability is a critical aspect, and assessing the cell deformation characteristics is essential for better diagnostics of healthy and deteriorating RBCs. There is a need to explore the connection between the cell deformation characteristics, cell morphology, disease states, storage lesion and cell shape-transformation conditions for better diagnostics and treatments. A numerical approach inspired from the previous research for RBC morphology predictions and for analysis of RBC deformations is proposed for the first time, to investigate the deformation characteristics of different RBC morphologies. The present study investigates the deformability characteristics of stomatocyte, discocyte and echinocyte morphologies during optical tweezers stretching and provides the opportunity to study the combined contribution of cytoskeletal spectrin network and the lipid-bilayer during RBC deformation. The proposed numerical approach predicts agreeable deformation characteristics of the healthy discocyte with the analogous experimental observations and is extended to further investigate the deformation characteristics of stomatocyte and echinocyte morphologies. In particular, the computer simulations are performed to investigate the influence of direct stretching forces on different equilibrium cell morphologies on cell spectrin link extensions and cell elongation index, along with a parametric analysis on membrane shear modulus, spectrin link extensibility, bending modulus and RBC membrane–bead contact diameter. The results agree with the experimentally observed stiffer nature of stomatocyte and echinocyte with respect to a healthy discocyte at experimentally determined membrane characteristics and suggest the preservation of relevant morphological characteristics, changes in spectrin link densities and the primary contribution of cytoskeletal spectrin network on deformation behaviour of stomatocyte, discocyte and echinocyte morphologies during optical tweezers stretching deformation. The numerical approach presented here forms the foundation for investigations into deformation characteristics and recoverability of RBCs undergoing storage lesion.

DOI

A 3D computational model of perfusion seeding for investigating cell transport and adhesion within a porous scaffold

Ziying Zhang, Jun Du, Zhengying Wei, Zhen Wang, Minghui Li, Jingda Ni

The process of cell seeding within a porous scaffold is an essential first step in the development of tissue-engineered bone grafts. Understanding the underlying mechanisms of cell distribution and adhesion is fundamental for the design and optimization of the seeding process. To that end, we present a numerical model to investigate the perfusion cell seeding process that incorporates cell mechanics, cell–fluid interaction, and cell–scaffold adhesion. The individual cells are modeled as deformable spherical capsules capable of adhering to the scaffold surface as well as to other cells with probabilistic bond formation and rupture. The mechanical deformation of the cell is calibrated with the stretching of mice mesenchymal stem cells induced by optical tweezers, while the predicted adhesive forces are consistent with the experimental data reported in the literature. A sub-domain is numerically reconstructed as the region of interest (ROI) which is representative of an actual scaffold. Through the simulations, the perfusion seeding kinetics within the ROI involving detailed transport and adhesion of cells over time is analyzed. The effects of the perfusion pressure and initial cell concentration on the seeding kinetics are studied in terms of adhesion rates, cell cluster formation, seeding uniformity, and efficiency, as well as scaffold permeability. The results highlight the importance of cell–fluid interaction and adhesion dynamics in modeling the dynamic seeding process. This bottom-up model provides a way to bridge detailed behaviors of individual cells to the seeding outcomes at the macroscopic scale, allowing for finding the best configuration to enhance cell seeding.

DOI

Red blood cell simulation using a coupled shell–fluid analysis purely based on the SPH method

Meisam Soleimani, Shahab Sahraee, Peter Wriggers
In this paper, a novel 3D numerical method has been developed to simulate red blood cells (RBCs) based on the interaction between a shell-like solid structure and a fluid. RBC is assumed to be a thin shell encapsulating an internal fluid (cytoplasm) which is submerged in an external fluid (blood plasma). The approach is entirely based on the smoothed particle hydrodynamics (SPH) method for both fluid and the shell structure. Both cytoplasm and plasma are taken to be incompressible Newtonian fluid. As the kinematic assumptions for the shell, Reissner–Mindlin theory has been introduced into the formulation. Adopting a total Lagrangian (TL) formulation for the shell in the realm of small strains and finite deflection, the presented computational tool is capable of handling large displacements and rotations. As an application, the deformation of a single RBC while passing a stenosed capillary has been modeled. If the rheological behavior of the RBC changes, for example, due to some infection, it is reflected in its deformability when it passes through the microvessels. It can severely affect its proper function which is providing the oxygen and nutrient to the living cells. Hence, such numerical tools are useful in understanding and predicting the mechanical behavior of RBCs. Furthermore, the numerical simulation of stretching an RBC in the optical tweezers system is presented and the results are verified. To the best of authors’ knowledge, a computational tool purely based on the SPH method in the framework of shell–fluid interaction for RBCs simulation is not available in the literature.

DOI

How should the optical tweezers experiment be used to characterize the red blood cell membrane mechanics?

Julien Sigüenza, Simon Mendez, Franck Nicoud

Stretching red blood cells using optical tweezers is a way to characterize the mechanical properties of their membrane by measuring the size of the cell in the direction of the stretching (axial diameter) and perpendicularly (transverse diameter). Recently, such data have been used in numerous publications to validate solvers dedicated to the computation of red blood cell dynamics under flow. In the present study, different mechanical models are used to simulate the stretching of red blood cells by optical tweezers. Results first show that the mechanical moduli of the membranes have to be adjusted as a function of the model used. In addition, by assessing the area dilation of the cells, the axial and transverse diameters measured in optical tweezers experiments are found to be insufficient to discriminate between models relevant to red blood cells or not. At last, it is shown that other quantities such as the height or the profile of the cell should be preferred for validation purposes since they are more sensitive to the membrane model.

DOI