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3D model of Cells and Simulation of Cell tractions
Physical forces generated by cells to its surrounding has been shown to be highly important to its function. In this project, 3D model of cells should be developed that can be used in simulations
The physical interaction between cells and the molecular structures of the extra cellular matrix (ECM) plays a crucial role in cell adhesion, growth, differentiation, migration and other cell functions and are hence linked to many biological processes, including inflammation, wound healing, embryogenesis, angiogenesis and metastasis. In the recent years, several approaches in traction force microscopy (TFM) were developed for the analysis, characterization and quantification of these cell traction forces. Through technical advantages and increasing computational power, it has become the standard and most developed approach to measure traction forces using image analysis of microscopy images obtained in vitro. These approaches can be split into a three-step process: - Visualize the movement induced by the cell traction forces with fluorescent micro beads embedded on the substrate - Use image analysis software to extract the displacement field from these images - Calculate the resulting traction force field with formulas obtained by continuum mechanics.
Due to the nature of the experiments and the resolution constraints by the scale of the system, calculating the traction forces is very sensitive to noise and the large parameter space of the process.
In our lab, a simulation environment based on Finite Element Analsysis and MATLAB has been developed to test different approaches in 2D. This framework should be extended to the third dimension.
In order to achieve this, accurate models of cells in 3D are used to simulate relevant cell tractions. In order to obtain these models, tools are needed to transfer 3D microscopy stacks into real models of the cells. Once 3D models have been obtained, they can serve as inputs for simulating traction forces.
The physical interaction between cells and the molecular structures of the extra cellular matrix (ECM) plays a crucial role in cell adhesion, growth, differentiation, migration and other cell functions and are hence linked to many biological processes, including inflammation, wound healing, embryogenesis, angiogenesis and metastasis. In the recent years, several approaches in traction force microscopy (TFM) were developed for the analysis, characterization and quantification of these cell traction forces. Through technical advantages and increasing computational power, it has become the standard and most developed approach to measure traction forces using image analysis of microscopy images obtained in vitro. These approaches can be split into a three-step process: - Visualize the movement induced by the cell traction forces with fluorescent micro beads embedded on the substrate - Use image analysis software to extract the displacement field from these images - Calculate the resulting traction force field with formulas obtained by continuum mechanics.
Due to the nature of the experiments and the resolution constraints by the scale of the system, calculating the traction forces is very sensitive to noise and the large parameter space of the process.
In our lab, a simulation environment based on Finite Element Analsysis and MATLAB has been developed to test different approaches in 2D. This framework should be extended to the third dimension.
In order to achieve this, accurate models of cells in 3D are used to simulate relevant cell tractions. In order to obtain these models, tools are needed to transfer 3D microscopy stacks into real models of the cells. Once 3D models have been obtained, they can serve as inputs for simulating traction forces.
ollowing steps should be achieved: - Literature review - Tool development to generage 3D cell models from microscopy stacks - Cell traction simulations using Finite Elements and MATLAB. - Documentation
ollowing steps should be achieved: - Literature review - Tool development to generage 3D cell models from microscopy stacks - Cell traction simulations using Finite Elements and MATLAB. - Documentation
Claude Holenstein, claude.holenstein@hest.ethz.ch, ETH Zürich / Professorship Dr. Jess Snedeker
Claude Holenstein, claude.holenstein@hest.ethz.ch, ETH Zürich / Professorship Dr. Jess Snedeker