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Title: Viscoelastic finite element modeling of deformation transients of single cells
Author: Teo, Soo Kng
ISNI:       0000 0001 3516 1849
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2008
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The objective of this thesis is to use computational modeling to study the deformation of single cells subjected to mechanical stresses. Our motivation stems from experimental observations that cells are subjected to mechanical stresses arising from their environment throughout their lifetime, and that such stresses can regulate many important biological processes. While the exact mechanotransduction mechanisms involved are not well understood, quantitative models for cell deformation can yield important insights. In this thesis, we developed an axisymmetric finite element model to study the deformation of suspended fibroblasts in the optical stretcher and neutrophils in tapered micropipettes. The key feature of our model is the use of a viscoelastic constitutive equation whose parameters can be varied both spatially and temporally so as to mimic the experimentally-observed spatio-temporal heterogeneity of cellular material properties. Our model suggested that cellular remodeling, in the form of an increased cellular viscosity, occurred during optical stretching of fibroblasts. The increase would have to be approximately 20-fold to explain the experimental data for different loading time-scales. We also showed that cell size is a more important factor in determining the strain response of the optically-stretched fibroblasts compared to the thickness of the actin cortical region. This result can explain the higher optical deformability observed experimentally for malignant fibroblasts. In addition, our simulations showed that maximal stress propagates into the nuclear region for malignant fibroblasts whereas for normal fibroblasts, the maximal stress does not. Finally, results from modeling the tapered micropipette experiments also suggested that cellular remodeling, in the form of a decreased cellular elasticity and viscosity, occurred during the process of neutrophil aspiration. Taken together, our simulation results on optically-stretched fibroblasts and aspirated neutrophils suggested that cells in general are able to sense mechanical stresses and respond by varying their material properties during deformation.
Supervisor: Goryachev, Andrew ; Parker, Kim ; Hwee, Chiam Keng Sponsor: Agency of Science, Technology and Research
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral