Mechanical Responses of Breast Cancer Cells to Substrates of Varying Stiffness Revealed by Single-Cell Measurements

Abstract

How cancer cells respond to different mechanical environments remains elusive. Here, we investigated the tension in single focal adhesions of MDA-MB-231 (metastatic breast cancer cells) and MCF-10A (normal human breast cells) cells on substrates of varying stiffness using single-cell measurements. Tension measurements in single focal adhesions using an improved FRET-based tension sensor showed that the tension in focal adhesions of MDA-MB-231 cells increased on stiffer substrates while the tension in MCF-10A cells exhibited no apparent change against the substrate stiffness. Viscoelasticity measurements using magnetic tweezers showed that the power-law exponent of MDA-MB-231 cells decreased on stiffer substrates whereas MCF-10A cells had similar exponents throughout the whole stiffness, indicating that MDA-MB-231 cells change their viscoelasticity on stiffer substrates. Such changes in tension in focal adhesions and viscoelasticity against the substrate stiffness represent an adaptability of cancer cells in mechanical environments, which can facilitate the metastasis of cancer cells to different tissues.

Functions and clinical significance of mechanical tumor microenvironment: cancer cell sensing, mechanobiology and metastasis

“…They found that cholangiocyte differentiation was regulated by matrix proteins and stiffness properties, and revealed the roles of ERK and Rho-associated protein kinase (ROCK) during the differentiation process. In another study, Tian et al [80] mimicked the matrix stiffness of different tissues from soft brain to stiff bone using PA substrates and probed the mechanical responses of breast cancer cells against diverse stiffnesses using magnetic tweezers and advanced imaging techniques. To overcome the inherent limitations of a continuous elastic substrate, substrates consisting of micropillars were developed.…”

“…In another study, Tian et al . [80] mimicked the matrix stiffness of different tissues from soft brain to stiff bone using PA substrates and probed the mechanical responses of breast cancer cells against diverse stiffnesses using magnetic tweezers and advanced imaging techniques. To overcome the inherent limitations of a continuous elastic substrate, substrates consisting of micropillars were developed.…”

Cell and Tissue Nanomechanics: From Early Development to Carcinogenesis

“…It was shown that the nanomechanics of tumor cells depends on the rigidity of the substrate. Metastatic breast cancer cells are able to adapt to the stiffness of the matrix, increasing their elasticity, which allows them to survive in tissues with varying rigidity [ 136 ]. A similar change in cell stiffness has also been demonstrated in bladder tumor cells [ 134 ].…”

Biophysical interactions between components of the tumor microenvironment promote metastasis

“…Biophysical measurements comparing the mechanical responses of normal and cancer cells have proven that cancer cells seem to become more compliant than their normal counterparts. The increased deformability of malignant cells is directly related with an increased metastatic potential (Tian et al 2020 ). In cancer cells, a softer cytoplasm correlates with a less-organized cytoskeleton (Guck et al 2005 ; Cross et al 2007 ).…”