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Biological cells are able to sense the stiffness, geometry and topography of their environment and sensitively respond to it. For this purpose, they actively apply contractile forces to the extracellular space, which can be determined by traction force microscopy. Thereby cells are cultured on elastically deformable substrates and cellular traction patterns are quanti- tatively reconstructed from measured substrate deformations, by solving the inverse elastic problem. In this thesis we investigate the influence of environmental topography to cellular force generation and the distribution of intracellular tension. For this purpose, we reconstruct traction forces on wavy elastic substrates, using a novel technique based on finite element methods. In order to relate forces to single cell-matrix contacts and different structures of the cytoskeleton, we then introduce another novel variant of traction force microscopy, which introduces cell contraction modeling into the process of cellular traction reconstruction. This approach is robust against experimental noise and does not need regularisation. We apply this method to experimental data to demonstrate that different types of actin fibers in the cell statistically show different contractilities. We complete our investigation by simulation studies considering cell colonies and single cells as thermoelastically contracting continuum coupled to an elastic substrate. In particular we examined the effect of geometry on cellular behavior in collective cell migration and tissue invasion during tumor metastasis. |
