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Experiments and Inverse Analysis for Determining Non-Linear Viscoelastic Properties of Polymeric Capsules and Biological Cells.

By Nhung T. Nguyen


In this thesis, the mechanics of polymeric capsules and biological cells was studied using compression and atomic force microscopy (AFM), respectively. First, the force-time responses of fluid-filled polymeric capsules were acquired for ramp-reverse and ramp-hold loading. The compression process was simulated using finite element (FE) modeling, in which the capsule material is modeled by a non-linear viscoelastic (NLV) constitutive relationship. An inverse analysis based on surrogate modeling and a Kriging estimator is employed in order to address the computational cost issue associated with optimizing the error between the experimental data and the FE predictions. The method allows for the efficient extraction of the capsule wall's NLV parameters. This study on polymeric capsules is a precursor to a study on biological cells, using AFM indentation technique to investigate the correlation between the cells’ NLV properties and alterations in the cytoskeletal structures. Two approaches were utilized. In the first, breast cancer cells at the benign (MCF-10A) and malignant (MCF-7) states were indented using spherical probes in AFM contact mode in fluid. A two-step indentation loading input was employed. It was comprised of applying a small force to initiate the contact between the probe and the cell, followed by controlling the AFM piezo movement in ramp-reverse and ramp-hold loading. The force-time responses of the cells were recorded and used for the extraction of the mechanical properties. The indentation experiment was also simulated using the FE method, and the same inverse technique (surrogate modeling with a Kriging estimator) was applied to extract the NLV properties of MCF-10A and MCF-7 cells. In the second, MCF-10A cells treated with the drug cytochalasin D to disrupt the cytoskeleton structure were studied, and their NLV parameters were characterized through the same procedure. Comparison between the extracted NLV properties indicates that malignant cells (MCF-7) are softer and exhibit more relaxation. Disrupting the cytoskeleton using the drug cytochalasin D also results in a larger amount of relaxation in the cell's response. These results may be useful for disease diagnosing purposes

Topics: Experiments and Inverse Analysis for Determining Non-Linear Viscoelastic Properties of Polymeric Capsules and Biological Cells
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