Glioma cells in vitro display liquid crystal characteristics

Glioblastomas (GBM) are the most common adult brain tumors, characterized by rapid invasion into the normal brain and therapeutic resistance. We have previously shown that GBM tumors exhibit self-organized, nematically aligned, multicellular structures, termed "oncostreams," that influence tumor invasion and malignancy. To further understand oncostream dynamics and the biomechanical interactions between glioma cells and the ECM we established a novel in vitro system. Time-lapse imaging revealed the presence of topological defects in the GBM cultures. Two types of topological defects were mainly found in the system: comets (+1/2 charge) and trefoils (-1/2 charge). Our investigation of topological defects aims to reveal their potential functions within brain tumors related to cancer cell invasion, collective migration, and apoptosis. Our results show, on average, high levels of apoptosis within the trefoil defect core and at the head of comet defects. This also impacts local cell density, with about 40% fewer cells at the trefoil core compared to elsewhere in the culture. Future work aims to study this phenomenon in 3D, utilizing a gel platform to allow for the hypothesized migration upwards at defect sites. Our results demonstrate that glioma cells grown in vitro behave as liquid crystals. Our data will define novel physical functional structures in GBMs, leading to the development of therapeutic strategies targeting oncostreams and topological defects.