The effect of neighboring cells on the stiffness of cancerous and non-cancerous human mammary epithelial cells

Abstract

Using an Atomic Force Microscope (AFM) with a 5.3 μm diameter spherical probe, we determined mechanical properties of individual human mammary epithelial cells. The cells were derived from a pair of cell lines that mimic cell progression through four phases of neoplastic transformation: normal (nontransformed), immortal, tumorigenic, and metastatic. Measurements on cells in all four phases were taken over both the cytoplasmic and nuclear regions. Moreover, the measurements were made for cells in different microenvironments as related to cell-cell contacts: isolated cells; cells residing on the periphery of a contiguous cell monolayer; and cells on the inside of a contiguous cell monolayer. By fitting the AFM force versus indentation curves to a Hertz model, we determined the pseudo-elastic Young's modulus, E. Combining all data for the cellular subregions (over nucleus and cytoplasm) and the different cell microenvironments, we obtained stiffness values for normal, immortal, tumorigenic, and metastatic cells of 870 Pa, 870 Pa, 490 Pa, and 580 Pa, respectively. That is, cells become softer as they advance to the tumorigenic phase and then stiffen somewhat in the final step to metastatic cells. We also found a distinct contrast in the influence of a cell's microenvironment on cell stiffness. Normal mammary epithelial cells inside a monolayer are stiffer than peripheral cells, which are stiffer than isolated cells. However, the microenvironment had a slight, opposite

Mechanical properties of normal versus cancerous breast cells

“…While our MSDs are comparable to MSDs previously determined by particle-tracking experiments in breast cells, our values of G are several orders of magnitude smaller than measurements by AFM indentation (500–2000 Pa) even on the same cell types (Li et al 2009; Lee et al 2012; Network TPS-OC 2013; Guo et al 2014b). The discrepancy probably arises because these techniques probe distinct structures within the cell.…”

Mechanical Heterogeneity in Tissues Promotes Rigidity and Controls Cellular Invasion

“…Recent experimental evidence [15][16][17][18] have revealed that tumor cells exhibit a broad distribution of various biomechanical properties. These include intra-tumor heterogeneity in cell stiffnesses [17,[19][20][21][22], stresses, and cell-cell interactions [21,23]. However, there is no consensus on how these heterogeneities affect the mechanical behavior at the tissue level.…”

Atomic Force Microscopy in Characterizing Cell Mechanics for Biomedical Applications: A Review

“…For example, the tumor microenvironment is composed of blood and lymphatic vessels and a variety of nonmalignant host cells, including fibroblasts, monocytes, macrophages, mast cells, mesenchymal stem cells and so on [89], [90]. Recent studies have shown that cell-cell contacts have a significant effect on cell mechanics [91]- [93]. In 2014, Guo et al [91] applied AFM to investigate the mechanical properties of cells in three different microenvironments as related to cell-cell contacts, including isolated cells, cells residing on the periphery of a contiguous cell monolayer, and cells on the inside of a contiguous cell monolayer.…”

“…Recent studies have shown that cell-cell contacts have a significant effect on cell mechanics [91]- [93]. In 2014, Guo et al [91] applied AFM to investigate the mechanical properties of cells in three different microenvironments as related to cell-cell contacts, including isolated cells, cells residing on the periphery of a contiguous cell monolayer, and cells on the inside of a contiguous cell monolayer. The results showed that the stiffness of cancer cells was less sensitive to the microenvironment than normal cells.…”