Abstract
A cell’s mechanical properties are important in determining its adhesion, migration, and response to the mechanical properties of its microenvironment and may help explain behavioral differences between normal and cancerous cells. Using fluorescently labeled peroxisomes as microrheological probes, the interior mechanical properties of normal breast cells were compared to a metastatic breast cell line, MDA-MB-231. To estimate the mechanical properties of cell cytoplasms from the motions of their peroxisomes, it was necessary to reduce the contribution of active cytoskeletal motions to peroxisome motion. This was done by treating the cells with blebbistatin, to inhibit myosin II, or with sodium azide and 2-deoxy-\(\textsc {d}\)-glucose, to reduce intracellular ATP. Using either treatment, the peroxisomes exhibited normal diffusion or subdiffusion, and their mean squared displacements (MSDs) showed that the MDA-MB-231 cells were significantly softer than normal cells. For these two cell types, peroxisome MSDs in treated and untreated cells converged at high frequencies, indicating that cytoskeletal structure was not altered by the drug treatment. The MSDs from ATP-depleted cells were analyzed by the generalized Stokes–Einstein relation to estimate the interior viscoelastic modulus \(G^{*}\) and its components, the elastic shear modulus \(G^{\prime }\) and viscous shear modulus \(G^{\prime \prime }\), at angular frequencies between 0.126 and 628 rad/s. These moduli are the material coefficients that enter into stress–strain relations and relaxation times in quantitative mechanical models such as the poroelastic model of the interior regions of cancerous and non-cancerous cells.
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Acknowledgments
The authors thank K. Scarpinato and J. Jarzen for providing HMLER cells and insights on their culture, S. Fahrbach for the use of her luminometer for ATP assays, and L. McDonald and G. Marrs for high-resolution confocal fluorescence microscopy images of actin stress fibers in breast epithelial cells. The authors thank D. Lyles for comments on this manuscript. This material is based upon work supported by the National Science Foundation under Grant Number 1106105 (JM, KB, and GH). AMS was supported by National Institutes of Health (T32GM095440) and National Science Foundation (0907738) Grants.
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Smelser, A.M., Macosko, J.C., O’Dell, A.P. et al. Mechanical properties of normal versus cancerous breast cells. Biomech Model Mechanobiol 14, 1335–1347 (2015). https://doi.org/10.1007/s10237-015-0677-x
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DOI: https://doi.org/10.1007/s10237-015-0677-x