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UBC Theses and Dissertations

Modeling biomechanical responses of cells to external forces Wu, Tenghu

Abstract

For many cells, their biomechanical properties are important to their biofunctions. This thesis contains three computational studies of cellular dynamics under mechanical deformation. When infected by malaria, infected red blood cells (iRBCs) become less deformable and tend to block microcapillaries. Microfluidic channels have been used to investigate the deformability of iRBC at different infection stages. In my first project, I applied a discrete iRBC model to simulate the traverse of iRBCs through a microfluidic channel and investigated the progressive loss of the cell deformability due to three factors: the membrane stiffening, the cell surface-volume ratio reduction, and the parasite growing inside the cell. The results indicate that the growth of the parasite clusters play the most significant role in causing the channel blockage. Recent experiments have investigated the response of neutrophils after passing through microfluidic channels. The results indicate that neutrophils may be activated by mechanical deformation. Mechanical deformation causes disassembly of the cytoskeletal network of the neutrophils, which results in a sudden drop of the cell elastic modulus (termed fluidization). The fluidization is followed by either activation of the neutrophils with formation of pseudopods or uniform recovery of the cytoskeletal network without pseudopod formation. The former only occurs when the neutrophils' transit rate is slow. I proposed a chemo-mechanical model for the fluidization and activation processes, based on the polarization of the Rac protein through a wave-pinning mechanism. The model captures the main features of the experimental observation. The third project investigates the response of smooth muscle cells to transient stretch-compress (SC) and compress-stretch (CS) maneuvers. Prior experimental results indicate that the transient SC maneuver causes a sudden fluidization of the cell while the CS maneuver does not. To understand this asymmetric behavior, I built a biomechanical model to probe the response of stress fibers to the two maneuvers. The model couples the cross-bridge cycle of myosin motors with a viscoelastic Kelvin-Voigt element. Simulation results point to the sensitivity of the myosin detachment rate to tension as the cause for the asymmetric response of the stress fiber to the CS and SC maneuvers.

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Attribution 2.5 Canada

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