Reconstruction and Simulation of Cellular Traction Forces

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

An analysis of the performance of a South African stainless steel manufacturer in localising the demand for corrosion resistant steels within the Eastern Cape catalytic converter industry

Commercial decisions are been made with respect to the competitive advantage of manufacturing catalytic converters in South Africa. This thesis identifies those factors relating to the sourcing of stainless steel and the impact it has of securing future business in a competitive environment. The catalytic converter industry requires the support of a stainless steel plant that provides high quality products at a competitive price, while keeping abreast with international developments

Model-based Traction Force Microscopy Reveals Differential Tension in Cellular Actin Bundles

Adherent cells use forces at the cell-substrate interface to sense and respond to the physical properties of their environment. These cell forces can be measured with traction force microscopy which inverts the equations of elasticity theory to calculate them from the deformations of soft polymer substrates. We introduce a new type of traction force microscopy that in contrast to traditional methods uses additional image data for cytoskeleton and adhesion structures and a biophysical model to improve the robustness of the inverse procedure and abolishes the need for regularization. We use this method to demonstrate that ventral stress fibers of U2OS-cells are typically under higher mechanical tension than dorsal stress fibers or transverse arcs.</p

Junge Erwachsene und die Pandemie: Erkenntnisse der CILS4COVID-Befragung

Junge Menschen in Deutschland verhalten sich überwiegend verantwortungsvoll und sorgen sich um andere – sie sind nicht die Problemgruppe, als die sie von Medien und Politik oftmals dargestellt werden

Generation of contractile actomyosin bundles depends on mechanosensitive actin filament assembly and disassembly

Adhesion and morphogenesis of many non-muscle cells are guided by contractile actomyosin bundles called ventral stress fibers. While it is well established that stress fibers are mechanosensitive structures, physical mechanisms by which they assemble, align, and mature have remained elusive. Here we show that arcs, which serve as precursors for ventral stress fibers, undergo lateral fusion during their centripetal flow to form thick actomyosin bundles that apply tension to focal adhesions at their ends. Importantly, this myosin II-derived force inhibits vectorial actin polymerization at focal adhesions through AMPK-mediated phosphorylation of VASP, and thereby halts stress fiber elongation and ensures their proper contractility. Stress fiber maturation additionally requires ADF/cofilin-mediated disassembly of non-contractile stress fibers, whereas contractile fibers are protected from severing. Taken together, these data reveal that myosin-derived tension precisely controls both actin filament assembly and disassembly to ensure generation and proper alignment of contractile stress fibers in migrating cells.Peer reviewe