title: Tumor invasion optimization by mesenchymal-amoeboid heterogeneity.
abstract: Metastasizing 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.
authors.affiliation: School of Physics and Astronomy, The Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Inbal
authors.initials: I
authors.lastname: Hecht
authors.affiliation: School of Physics and Astronomy, The Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Bar-El
authors.affiliation: Chair of Systems Design, ETH (Eidgenoessische Technische Hochschule) Zurich, Weinbergstrasse 58, 8092 Zurich, Switzerland.
authors.forename: Frederic
authors.initials: F
authors.lastname: Balmer
authors.affiliation: Department of Clinical Microbiology, Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Sari
authors.initials: S
authors.lastname: Natan
authors.affiliation: Department of Clinical Microbiology, Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Ilan
authors.initials: I
authors.lastname: Tsarfaty
authors.affiliation: Chair of Systems Design, ETH (Eidgenoessische Technische Hochschule) Zurich, Weinbergstrasse 58, 8092 Zurich, Switzerland.
authors.forename: Frank
authors.initials: F
authors.lastname: Schweitzer
authors.affiliation: School of Physics and Astronomy, The Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 6997801, Israel.|Center for Theoretical Biological Physics, Rice University, Houston, TX 77005-1827, USA.
authors.forename: Eshel
authors.initials: E
authors.lastname: Ben-Jacob
mesh_terms: D016000:Cluster Analysis; D058750:Epithelial-Mesenchymal Transition; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008962:Models, Theoretical; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000473:pathology; D013816:Thermodynamics