Abstract 3766: Mechanical properties of cancer cells: a possible biomarker for stemness.

Abstract

Abstract There is evidence that mechanical properties and deformability can be used as a biomarker to distinguish between healthy and cancerous cells. A number of biophysical techniques such as atomic force microscopy (AFM), and optical tweezers have been used to measure the mechanical properties of cancer cells. Deformability of a whole cell, which depends on the properties of the cytoplasm, the cytoskeleton and the nucleus, can be defined in terms of the strain response of the cell to an applied stress. Two different cell mechanical behaviors have been observed: 1) circulating white blood cells behave as liquid drops with a cortical tension; 2) most tissue cells behave as viscoelastic solids. In this study, micropipette aspiration was used to investigate deformability differences between two breast cancer cell lines: BT-20 and Hs578T. Hs578T breast cancer cells have been reported to have a stem-like phenotype, whereas BT-20 cells are more recognized as being non-stem-like. Cancer cells were aspirated one-by-one at controlled pressures into small glass micropipettes with radius, Rp, while the length of the aspirated section of the cell inside the micropipette, L, was measured. Two different aspiration procedures have been developed: 1) ramp test and 2) creep test. In the ramp test, suction pressure was increased linearly using a syringe pump, while for the creep test, the pressure was increased rapidly and then kept constant during the experiment. Using the ramp test, graphs of cell deformation (L/Rp) versus applied pressure, showed a linear trend for small deformations for both BT-20 and Hs578T cells, while for large deformations, the graphs were no longer linear. One explanation for this, was that above a deformation threshold the cells were exhibiting liquid-like behavior. This was tested using a constant aspiration pressure in the creep test. It was seen that half of the cells fully entered the micropipettes at constant pressure, a character of liquid drops, while the rest reached an equilibrium position, which implies a viscoelastic behavior for the cells. It could be concluded that for small deformations, cells mostly have solid-like behavior, while for large deformations they could exhibit liquid-like or viscoelastic behaviors. We also found that stem-like cancer cells are softer than non-stem-like cells with no significant differences between the mechanical properties of their cytoplasmic and nuclear regions, which allows them to deform more easily while undergoing extravasation and intravasation processes during metastasis. Our hypothesis is that the stem-like or non-stem-like phenotype of cancer cells is correlated with differences in mechanical properties. If these differences are significant enough, mechanical properties could be used as a biomarker for stemness of cells, which could eventually lead to a new diagnostic method in cancer research. This work was supported by grant CBET-1106118 from the National Science Foundation. Citation Format: Ameneh Mohammadalipour, Fabian Benencia, Monica M. Burdick, David F. J. Tees. Mechanical properties of cancer cells: a possible biomarker for stemness. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3766. doi:10.1158/1538-7445.AM2013-3766