(723b) Characterization and Modeling of Cancer Cell Motility in 3-D Extra-Cellular Matrix

Authors: 
Wu, P. H., Johns Hopkins University
Wirtz, D., Johns Hopkins University
Giri, A., Johns Hopkins Physical Sciences - Oncology Center
Sun, S. X., Johns Hopkins University



Cancer cell migration through the extra-cellular matrix (ECM) is one of the most important processes during metastasis. Cell migration is a multi-scale process, which integrates molecular kinetics and signaling; cell mechanics and microenvironment. A quantitative understanding of cell motion in three-dimensions will facilitate the development of a system-level understanding of cellular processes in cancer metastasis and further promote identification of new therapeutic targets. Though various mathematical models were proposed to measure cell migration on 2-D surfaces, adequate tools to characterize and model migration in 3-D are lacking. In this work, we observed the migration patterns of individual HT1080 fibrosarcoma cells on 2-D substrate and in 3-D collagen matrices for more than 8 hours. We found that non-Gaussian behavior of cell velocity distribution at various time scales in population level is a universal characteristic for both cell 2-D and 3-D migration and it is as result of the highly varied cell-to-cell motility behaviors. Further, cell velocity in 3-D matrices is anisotropic and velocity profiles display different speed and self-correlation processes at different directions. Together, by including cell-level variation, anisotropic velocity and observation noise in persistent random walk model, we were able to predict the population level of cell motility system in 3-D matrices which corresponding well to experimental observation. Our model further allows the estimation of speed for HT1080 cells in 3-D matrices at more pathophysiological relevant time scale (months) and we found there are small populations of cells that display ~10x higher speed than the general population and could imply that metastatic cells come from small populations of cells within a tumor.