Metastatic breast cancer cells adhere strongly on varying stiffness substrates, initially without adjusting their morphology

Abstract

We show that metastatic breast cancer cells are quantitatively identifiable from benign cells during adherence onto soft, elastic gels. We identify differences in time-dependent morphology and strength of adherence of single breast cells that are likely related to their malignancy and metastatic potential (MP). Specifically, we compare high and low MP breast cancer cells with benign cells as a control on collagen-coated, polyacrylamide gels with Young’s modulus in the physiological range of 2.4–10.6 kPa. We observe that the evaluated metastatic breast cancer cells remain rounded, with small contact area, up to 6.5 h following seeding. In contrast, the benign cells spread and become more elongated on stiffer gels. We identify measurable differences in the two-dimensional, lateral, traction forces exerted by the cells, where the rounded, metastatic cells apply significantly larger, traction forces, as compared to the benign cells, on gels stiffer than 2.4 kPa. The metastatic cell lines exhibited gel-stiffness-dependent differences in traction forces, strain energies, and morphologies during the initial stages of adhesion, which may relate to their MP or invasiveness.

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Acknowledgements

The authors thank Matthew Weinberg for his assistance with the statistical testing. The work was partially supported by the Technion EVPR Funds—the Elias Fund for Medical Research and the Karbeling Fund for Bio-Medical Engineering Research, and by a grant from the Ministry of Science, Technology and Space, Israel, and the National Science Council (NSC) of Taiwan.

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Correspondence to Daphne Weihs.

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Massalha, S., Weihs, D. Metastatic breast cancer cells adhere strongly on varying stiffness substrates, initially without adjusting their morphology. Biomech Model Mechanobiol 16, 961–970 (2017). https://doi.org/10.1007/s10237-016-0864-4

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Keywords

  • Mechanobiology
  • Cell adherence
  • Traction force microscopy
  • Fluorescence microscopy
  • Metastatic potential