Malignant brain tumors behave in vivo as liquid crystals: quasi long-range nematic order and topological defects.

Glioblastomas (GBM) are the most common adult brain tumors with worst prognosis, given their capacity to invade normal brain structures, and become resistant to all treatments. Our data demonstrated that GBM tumors exhibit self-organized, nematically aligned, multicellular structures, termed “oncostreams,” that influence tumor invasion and malignancy. GBM tumor cells grown in vitro exhibit topological defects and nematic correlation, defining GBMs as displaying liquid crystal organization. Using 3D brain reconstruction, we study how in-plane nematic alignment propagates in space throughout the tumor. Interestingly, nematic alignment length scale correlates with tumor aggression based on 4 unique mouse models and a human gliosarcoma patient. Ongoing work is utilizing whole brain clearing and light-sheet scanning microscopy to fully reconstruct 3D oncostream ordered organization and topological defects. We believe our work will demonstrate that GBMs in vivo behave as liquid crystals thus demonstrating a novel ordering of malignant brain tumors. This work will define the role of liquid crystal organization as novel physical structures in GBM, eventually leading to the development of therapeutic strategies targeting the structure underlying brain tumor organization, namely, the liquid crystalline order.