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Fractal Dimension of Breast Cancer Cell Migration in a Wound Healing Assay

Authors: R. Sullivan, T. Holden, G. Tremberger, Jr, E. Cheung, C. Branch, J. Burrero, G. Surpris, S. Quintana, A. Rameau, N. Gadura, H. Yao, R. Subramaniam, P. Schneider, S. A. Rotenberg, P. Marchese, A. Flamhlolz, D. Lieberman, T. Cheung


Migration in breast cancer cell wound healing assay had been studied using image fractal dimension analysis. The migration of MDA-MB-231 cells (highly motile) in a wound healing assay was captured using time-lapse phase contrast video microscopy and compared to MDA-MB-468 cell migration (moderately motile). The Higuchi fractal method was used to compute the fractal dimension of the image intensity fluctuation along a single pixel width region parallel to the wound. The near-wound region fractal dimension was found to decrease three times faster in the MDA-MB- 231 cells initially as compared to the less cancerous MDA-MB-468 cells. The inner region fractal dimension was found to be fairly constant for both cell types in time and suggests a wound influence range of about 15 cell layer. The box-counting fractal dimension method was also used to study region of interest (ROI). The MDAMB- 468 ROI area fractal dimension was found to decrease continuously up to 7 hours. The MDA-MB-231 ROI area fractal dimension was found to increase and is consistent with the behavior of a HGF-treated MDA-MB-231 wound healing assay posted in the public domain. A fractal dimension based capacity index has been formulated to quantify the invasiveness of the MDA-MB-231 cells in the perpendicular-to-wound direction. Our results suggest that image intensity fluctuation fractal dimension analysis can be used as a tool to quantify cell migration in terms of cancer severity and treatment responses.

Keywords: Higuchi fractal dimension, box-counting fractal dimension, cancer cell migration, wound healing.

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