Author : Melissa Lay Date : December 10, 2025
BME Ph.D. Defense:

Structure and Function of Active Nematic Liquid Crystal Order in Brain Tumors

Abstract: Glioblastomas (GBM) are the most common adult brain tumors, characterized by rapid invasion into the normal brain and therapeutic resistance. Our lab previously demonstrated that GBM tumors exhibit self-organized, nematically aligned, multicellular structures, termed “oncostreams,” that influence tumor invasion and malignancy. Oncostreams are regulated by collagen fibers and downregulation of collagen was shown to dismantle oncostream formation. This thesis aims to better characterize and understand the complex, heterogeneous nature of high-grade glioma tumors. 

In Chapter 2, I describe an in-vitro model utilized to study the dynamics of glioma oncostreams. I also show the presence of topological defects in this system. 2D topological defects are point-singularities where nematic order is abruptly disrupted. I explore the dynamics of topological defects in-vitro and their functional implications. I find that apoptosis and cell density are highly impacted at defect locations.

In Chapter 3, we move to 3D in-vivo tumors in both mouse models and human patient samples. 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. Creating 3D reconstructions and 3D elastic distortion maps allowed us to identify high nematic order domains (before called oncostreams) and to identify topological defects as regions of low nematic order and finite winding number using OpenViewMin. This is the first evidence of 3D topological defects in-vivo within tumors and highlights the complex liquid crystalline order of glioblastomas. Additionally, we find that these topological disclinations form various structures: closed loops with wedge, twist, or wedge-twist-wedge structures or lines starting or ending on blood vessels. 

In Chapter 4, I characterize the 3D in-vivo dynamics of glioma cells using patient-derived organoids and ex-vivo tissue slices of mouse gliomas. This enables us to prove that glioma tumors can be considered 3D active nematic liquid crystals, representing a key step forward in understanding their complex physical features. 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.