3D nematic organization and topological defects in brain tumors in vivo.

Glioblastomas (GBM) are the most common adult brain tumors, characterized by rapid invasion into the normal brain and therapeutic resistance. We previously demonstrated that GBM tumors exhibit self-organized, nematically aligned, multicellular structures, termed “oncostreams,” that influence tumor invasion and malignancy. Here we show the presence of topological defects in glioma cells in-vitro (2D) and tumors in-vivo (3D). To understand nematic organization and topological defects within gliomas in 3D, we utilized whole brain clearing and light-sheet scanning microscopy to image tumors with an extremely high resolution (0.5 x 0.5 x 0.5 um). Creating 3D reconstructions and 3D elastic distortion maps allowed us to identify oncostreams (high nematic order domains), and to identify topological defects as regions of low nematic order and finite winding number using OpenViewMin. To our knowledge, this is the first evidence of 3D topological defects in-vivo within tumors and highlights the complex liquid crystalline order of glioblastomas. We believe this new understanding of the structure of glioblastoma organization will lead to the development of therapeutic strategies targeting malignant oncostreams and topological defects.