A fludic material-based dynamic cell culture platform as an ex vivo disease model of breast cancer metastasis

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Through culturing the breast cancer cell line (MCF-7) on a viscous-dominant viscoelastic polymer substrate, it was demonstrated that stress relaxation time of the polymeric substrate is the dominant parameter that regulates the cell cycle arrest of non-invasive breast cancer cells. This research firstly reported that breast cancer cells can sense the material relaxation time at the range of milliseconds (80-290 ms). The viscous-dominant polymeric material induced the cellular senescence of breast cancer cellsthrough the generation of reactive oxygen species. Moreover, I was able to demonstrate that we can directly tune the the cellular fate of breast cancer cells by manipulating the molecular properties of the polymer (molecular weight distribution and molecular weight). The intracellular function and growth state of MCF7 cells are able to be manipulated by changing the molecular weight distribution (MWD) of a copolymer. Increasing the MWD (MWD > 1.5) promoted cell populations to form multicellular aggregates due to the decreasing bulk stress relaxation time of the substrate. The presence of low molecular weight polymer which results in MWD > 1.5 can switch the proliferative fate of breast cancer cells (MCF7) into cell cycle arrest fate accompanied by the generation of reactive oxygen species. Through those findings, I was also able to propose a new non-invasive method to distinguish the senescent cells from dormant cells and cells in normal-growth state based on the total protein content of cells through a phase difference by quantitative phase microscopy technique.