Hecht, InbalBar-El, YasminBalmer, FredericNatan, SariTsarfaty, IlanSchweitzer, FrankBen-Jacob, Eshel2017-05-152017-05-152015Hecht, Inbal, Bar-El, Yasmin, Balmer, Frederic, et al.. "Tumor Invasion Optimization by Mesenchymal-Amoeboid Heterogeneity." <i>Scientific Reports,</i> 5, (2015) Springer Nature: http://dx.doi.org/10.1038/srep10622.https://hdl.handle.net/1911/94262Metastasizing tumor cells migrate through the surrounding tissue and extracellular matrix toward the blood vessels, in order to colonize distant organs. They typically move in a dense environment, filled with other cells. In this work we study cooperative effects between neighboring cells of different types, migrating in a maze-like environment with directional cue. Using a computerized model, we measure the percentage of cells that arrive to the defined target, for different mesenchymal/amoeboid ratios. Wall degradation of mesenchymal cells, as well as motility of both types of cells, are coupled to metabolic energy-like resource level. We find that indirect cooperation emerges in mid-level energy, as mesenchymal cells create paths that are used by amoeboids. Therefore, we expect to see a small population of mesenchymals kept in a mostly-amoeboid population. We also study different forms of direct interaction between the cells, and show that energy-dependent interaction strength is optimal for the migration of both mesenchymals and amoeboids. The obtained characteristics of cellular cluster size are in agreement with experimental results. We therefore predict that hybrid states, e.g. epithelial-mesenchymal, should be utilized as a stress-response mechanism.engThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the articleﾒs Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.Journal articlehttp://dx.doi.org/10.1038/srep10622