Argento Anna E, Varela Maria L, Singh Gurveer, Visnuk Daiana P, Jacobovitz Binyamin, Rutherford Mary E, Edwards Marta B, Chaboche Quentin, Orringer Daniel A, Heth Jason A, Castro Maria G, Beller Daniel A, Blanch-Mercader Carles, Lowenstein Pedro R
Dept. of Biomedical Engineering, University of Michigan, Ann Arbor, USA.
Dept. of Neurosurgery, University of Michigan Medical School, Ann Arbor, USA.
bioRxiv. 2025 May 10:2025.04.14.648711. doi: 10.1101/2025.04.14.648711.
Active nematic liquid crystals are the main structural phase of gliomas, promoting collective migration and aggression. We establish the existence of nematic order and topological defect lines and loops in 3D in vivo mouse and human glioma brain tumors. As predicted by theory, sections through the disclination lines in 3D appear as ±1/2 topological defects in 2D. In 3D, these defects either persist along disclination lines or twist as they interconvert from -1/2 to +1/2. Cell alignment exhibits quasi-long-range order, spreading throughout the tumor over distances between 300-3000 m. In vitro -1/2 and +1/2 defects display changes in apoptosis levels, suggesting topological defects regulate glioma cell density. The large scale order of gliomas correlates with tumors' aggressive behavior. The organization of gliomas as active nematic liquid crystals provides a novel physical foundation of complex solid tumors; their deconstruction signposts potential treatments for deadly cancers.
活性向列相液晶是神经胶质瘤的主要结构相,促进集体迁移和侵袭。我们证实了在三维体内小鼠和人类神经胶质瘤脑肿瘤中存在向列序以及拓扑缺陷线和环。正如理论所预测的,三维中穿过向错线的截面在二维中表现为±1/2拓扑缺陷。在三维中,这些缺陷要么沿着向错线持续存在,要么在从-1/2转换为+1/2时发生扭曲。细胞排列呈现准长程有序,在整个肿瘤中传播的距离在300 - 3000微米之间。体外-1/2和+1/2缺陷显示凋亡水平发生变化,表明拓扑缺陷调节神经胶质瘤细胞密度。神经胶质瘤的大规模有序与肿瘤的侵袭性行为相关。神经胶质瘤作为活性向列相液晶的组织方式为复杂实体瘤提供了一种新的物理基础;对其解构为致命癌症的潜在治疗指明了方向。