Altered mechanical properties of actin fibers due to breast cancer invasion: parameter identification based on micropipette aspiration and multiscale tensegrity modeling.

Abstract

The biophysical properties of cells change with cancer invasion to fulfill their metastatic behavior. Cell softening induced by cancer is highly associated with alterations in cytoskeleton fibers. Changes in the mechanical properties of cytoskeletal fibers have not been quantified due to technical limitations. In this study, we used the micropipette aspiration technique to calculate and compare the viscoelastic properties of non-invasive and invasive breast cancer cells. We evaluated the mechanical properties of actin fibers and microtubules of two cancerous cell lines by using multiscale tensegrity modeling and an optimization method. Cancer invasion caused altered viscoelastic behavior of cells and the results of modeling showed changes in mechanical properties of major cytoskeleton fibers. The stiffness and viscosity constant of actin fibers in non-invasive cells were 1.28 and 2.27 times higher than those of the invasive cells, respectively. However, changes in mechanical properties of microtubules were minor. Immunofluorescent staining of fibers and their quantified distributions confirmed altered actin distribution among two cell lines, in contrast to microtubule distribution. This study highlights the function of cytoskeletal fibers in cancer progression, which could be of interest in designing therapeutic strategies to target cancer progress. Firstly, the viscoelastic behavior of non-invasive and invasive cells is examined with micropipette aspiration tests. A tensegrity model of cells is developed to mimic the viscoelastic behavior of cells, and tensegrity element stiffness is evaluated in an optimization procedure based on micropipette aspiration tests. Finally, by using immunofluorescent staining and confocal imaging, mechanical properties of actin filaments and microtubules of cancer cells are investigated during the course of metastasis.