EAPSI: Examining Cancer Cells' Response to the Shape and Stiffness of their Environment

Doss Bryant L, Tempe AZ

Investigators

Abstract

The behavior of single mammalian cells is strongly dependent on their growth environment. For example, cells grown on plastic surfaces will have different morphologies and movement mechanisms compared to cells that are grown on softer materials designed to resemble growth substrates in vivo. This effect is particularly important in cancer research because there is a high degree of interaction between a cancer cell and its local environment during invasion into nearby tissue. Understanding how cells react in different physical environments may lead to new therapeutic strategies to combat cancer metastasis. Dr. Keng-hui Lin at Academia Sinica in Taiwan has developed a technique to produce 3D scaffolds with adjustable stiffness and dimensions which may be used as a cell culture platform to study cell behavior under more physiological conditions. The goal of the project is to learn the scaffold technique under the supervision of Dr. Lin and apply the technique to study malignant breast cancer cells. This will provide local researchers a first-hand understanding of the 3D culture technique and will foster additional international collaborations. Recent studies using a combination of atomic force microscopy and confocal fluorescence microscopy on MDA-MB-231 breast cancer cells show a significant increase in Young's modulus as they invade into bovine collagen I hydrogels. This process is thought to be ROCK dependent, but it is unclear whether the cause is the 3D porous nature of the collagen or the act of invasion where the cells actively deform the collagen matrix. The goal of the project is to perform similar experiments on cells grown in the scaffolds to elucidate the basis of the observed cell stiffening. This NSF EAPSI award is funded in collaboration with the National Science Council of Taiwan.