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

Bonin, Keith

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title
The effect of neighboring cells on the stiffness of cancerous and non-cancerous human mammary epithelial cells
author
Guo, Xinyi
author
Bonin, Keith
author
Scarpinato, Karin
author
Guthold, Martin
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 (non-transformed), 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 effect on tumorigenic and little effect on immortal and metastatic cell stiffness. Thus, the stiffness of cancer cells is less sensitive to the microenvironment than normal cells. Our results show that the mechanical properties of a cell can depend on cancer progression and microenvironment (cell–cell interactions).
The authors acknowledge funding from the Armed Forces Institute of Regenerative Medicine (AFIRM) and grant support from the Wake Forest Center for Molecular Communication and Signaling (U01057). This material is based upon work supported by the National Science Foundation under Grant Number 1106105 (KB and MG). (sponsorship)
subject
human mammary epithelial cells
neoplastic transformation
cell microenvironments
cell stiffness
citation
16 (volume)
date
2015-10-09T17:47:23Z (accessioned)
2015-10-09T17:47:23Z (available)
2014 (issued)
identifier
http://hdl.handle.net/10339/57371 (uri)
identifier
http://dx.doi.org/10.1088/1367-2630/16/10/105002 (doi)
publisher
IOP Science
rights
https://creativecommons.org/licenses/by/3.0/ (uri)
source
New Journal of Physics
type
Article

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