Evaluating the mechanical properties of biological cells in their living state is of upmost importance for understanding cellular behavior in health or disease and in particular cancer cells. In recent years, force microscopy and spectroscopy have become inevitable tools to attain the elastic modulus of cells as a whole using colloidal probes or with high lateral precision by sharp tips. However, the obtained values have to be treated with due care to avoid data misinterpretation. Here, we present a comparison of elasticity between four metastatic cancer cell lines (lung, liver, skin, and breast epithelial-type cancer cells) taken by colloidal and sharp probes using force spectroscopy on cell monolayers and stress the impact of a stiff substrate, which cells are attached to, on the measured values especially in cancerous cells, which depict abnormalities in structure and cellular components. As a result of our analysis, we suggest to solely use sharp probes for the mechanical characterization of cancer cells when the force-distance relation is fit by a conventional contact mechanics model such as the Hertz model.

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