Glioblastoma Brain Tumors Organize as Active Nematic Liquid Crystals with Novel Implications

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 characteristics of active nematic liquid crystals: nematic order, topological defects, and quasi-long-range order (Argento et al. 2025). The degree of nematic order also scales with tumor aggression - the most malignant tumors are the most nematically organized. Now, we aim to investigate the function of topological defects both in 2D and 3D, in-vitro and in-vivo. In-vitro, we find that topological defects are highly correlated with apoptotic processes, measured both with time-lapse confocal imaging and high-resolution spatial RNA transcriptomics analysis. Additionally, we utilize whole brain clearing, immunofluorescence, and light-sheet scanning microscopy to identify regions of apoptosis in 3D in-vivo mouse and human tumors. By identifying topological defects as epicenters of apoptosis, we distinguish targets to modulate glioma cell survival in-vitro and in-vivo. Future work aims to utilize colloids and liquid crystal elastomers to enhance glioma cell death at defect regions. We believe this new understanding of the structure of glioblastoma organization will lead to the development of therapeutic strategies targeting malignant nematic order and topological defects.