Breast cancer cells and substrate stiffness


Cells sense stiffness of surrounding tissues and adapt their activity, proliferation, motility and mechanical properties based on such interactions. Cancer and other diseases alter stiffness of tissues, and the response of cancer cells to this stiffness can also be affected.

The goal of this study was to analyse the effects of substrate elasticity on the mechanical properties of MCF-7 breast cancer cells. For this, MCF-7 cells were plated on polyacrilamide gels of varying stiffness (0.1 – 264 kPa) and their elastic and viscoelastic properties were measured using Atomic Force Microscopy (AFM).

The Apparent Young’s Modulus was derived from the indentation of the cells, while a second exponential decay was used to fit the stress-relaxation pause segment in order to calculate the viscoelastic parameters based on a Zener model of the cell. Confocal microscopy was employed to visualize the morphology and actin cytoskeleton of the cells.

Such experiments showed that MCF-7 cells seeded on polyacrylamide gels have the ability to detect the stiffness of the substrate and alter their mechanical properties in response. MCF-7 cells plated on soft substrates display lower stiffness and viscosity when compared to those seeded on stiffer gels or glass. These differences can be associated with differences in the morphology and cytoskeleton organisation, since cells seeded on soft substrates have a round morphology while cells seeded on stiffer substrates acquire a flat and spread morphology with formation of actin filaments, similar to that observed when seeded on glass. In conclusion, these findings contribute to the unravelling of the mechanotransduction machinery of breast cancer cells, showing that even low invasive cells, such as MCF-7 cells, can detect the stiffness of the surrounding tissue and alter their mechanical properties accordingly. Tumour microenvironment and the mechanical properties of the tissue acquire an important role in the mechanical properties of breast cancer cells and, in consequence, in their ability to invade other tissues, with important implications for disease progression.

Substrate stiffness modulates the viscoelastic properties of MCF-7 cells; by Juan Carlos Gil-Redondo, Andreas Weber, Barbara Zbiral, Maria dM. Vivanco, José L. Toca-Herrera

Findings of this work have been published in: Journal of the Mechanical Behavior of Biomedical Materials, Volume 125, January 2022; https://doi.org/10.1016/j.jmbbm.2021.104979


In connection with the present studies, previous work of the research group at the Institute of Biophysics evidence the importance of tumour microenvironment int the mechanical properties of breast cancer cells:

Further evidence for the role of estrogen signaling in breast cancer, Materials 2021, 14(11), 2897; https://doi.org/10.3390/ma14112897

Time- and Zinc-Related Changes in Biomechanical Properties of Human Colorectal Cancer Cells Examined by Atomic Force Microscopy, Biology 2020, 9 (12) 468; https://doi.org/10.3390/biology9120468

Single-Cell Probe Force Studies to Identify Sox2 Overexpression-Promoted Cell Adhesion in MCF7 Breast Cancer Cells, Cells 2020, 9(4), 935; https://doi.org/10.3390/cells9040935

Resveratrol-Induced Temporal Variation in the Mechanical Properties of MCF-7 Breast Cancer Cells Investigated by Atomic Force Microscopy, International Journal of Molecular Sciences 2019, 20(13), 3275; https://doi.org/10.3390/ijms20133275

 


06.12.2021