Liquid Crystal-like Self-Organization of Glioblastoma Prevents Cell Density Induced Migratory Arrest

Abstract Glioblastoma is the most lethal and frequent type of primary brain tumors, characterized by a high proliferative and infiltrative capacity, leading to frequent recurrences after therapy. Here, we used live cell imaging to analyze the effect of cell density variations on the migratory capacity of established and primary glioblastoma cell lines. We found that proliferation events promoted local velocity of glioblastoma cells, but had only a small effect on large spatial scales. Furthermore, two phenotypes were found when subjecting glioblastoma cells to cell density gradient. One phenotype was characterized by the active migration of cells, independent of proliferation, while the other was mostly driven by cell proliferation. Lastly, the analysis of effects of an overall increasing cell density demonstrated that cells showing signs of self-organization, forming liquid crystal-like structures, are able to escape the expected cell-density induced migratory arrest. Notably, the emergence of small-scale liquid crystal-like order was associated with a promotion of cellular migration, even in cell populations that were largely in a state of migratory arrest. Thus, structure formation could help glioblastoma cells to move efficiently in states of high confinement, maintaining infiltrative properties. Competing Interest Statement The authors have declared no competing interest. Footnotes E-mail: U.H.: urszula.hohmann{at}medizin.uni-halle.de, C.G.: chalid.ghadban{at}medizin.uni-halle.de, J.P.: julian.prell{at}uk-halle.de, C.S.: christian.strauss{at}uk-halle.de, F.D.: faramarz.dehghani{at}medizin.uni-halle.de, T.H.: tim.hohmann{at}medizin.uni-halle.de Correction of grammar and spelling, improved readability. Merging of figures 6 and 7 of the previous version.