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A particle-based model for computing fluid flows and cell dynamics

University of British Columbia

The connection between certain human diseases and changes in the mechanical properties of living cells is well established, e.g. in the cases of malaria and cancer. However, the mechanism for the mechanical modifications, which tend to facilitate the pathogenesis of such diseases, is not always clear. For instance, the overall loss of deformability of malaria-infected red blood cells (RBCs) corresponds to a 10-fold increase in the rigidity of the cell membrane. On the other hand, micropipette aspiration has only measured a 3-fold increase in the elastic modulus. In this thesis, a particle-based model is developed to explore the interplay between the underlying microstructures and the behavior of the cell as a whole. The research consists of three related projects. The first project deals with the long-standing problem of Smoothed Particle Hydrodynamics (SPH) method with open boundaries and solid walls. We propose a "rotational pressure-correction scheme" with a consistent pressure boundary condition that leads to a large improvement in accuracy of calculated pressure and the drag coefficient on solid obstacles. The second and third projects concern developing a 2D and then 3D particle-based model for RBCs to explore the parasite-driven changes in malaria-infected RBCs. In our models the cell membrane is replaced by a set of discrete particles connected by linear or nonlinear springs. In addition, a linear bending elasticity is implemented using the deviation of the local curvature from the innate curvature of the biconcave shape of a resting RBC. The cytoplasm and the external liquid are modelled as homogeneous Newtonian fluids, and discretized by particles as in standard SPH solution of the Navier-Stokes equations. The malaria parasite is modelled as an aggregate of particles constrained to rigid-body motion. We argue that the discrepancy in the estimated elastic modulus of the membrane is caused by the presence of the rigid parasite particles inside infected cells, and have carried out numerical simulations to demonstrate this mechanism. Our three-dimensional simulation of RBC stretching tests by optical tweezers accurately demonstrates the compensating effects between the existence of malaria parasites and the elevated stiffness of the membrane on the overall deformability of infected RBC.

Text

2012-04-23

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/42186

Chemical and Biological Engineering

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/