Monitoring of astroglial water channel protein’s structure and function

Aquaporin-4 (AQP4) is the most abundant water channel in the central nervous system, localized predominantly in the perivascular end-feet of astrocytes, where it plays a key role in maintaining water homeostasis. AQP4 exists as hetero-tetramers composed of its two major isoforms, M1 and M23, and has the capacity to form Orthogonal Arrays of Particles (OAPs), with the size of these aggregates determined by the M1:M23 ratio. This thesis investigates how AQP4, through both its general functions and its aggregation into OAPs, influences cellular behaviour across contexts of neural development, glioma progression, and biomaterial applications supporting astrocyte activity. Our findings demonstrate that AQP4's aggregation state impacts neural stem cell proliferation, migration, and viability in the developing brain, highlighting its role in the mechanobiology of these cells. In glioblastoma, altered AQP4 expression and OAP localization modulate tumour migration, invasiveness and matrix metalloproteinase activity, with larger OAPs significantly reducing glioma cell invasiveness. Extending our investigation to glial biomaterial engineering, we explore electrospun polyvinyl alcohol/gelatine nanofibers as a biomaterial scaffold that promotes astrocyte adhesion, survival, and alignment. Fiber orientation in these scaffolds plays a critical role in guiding astrocyte organization, offering potential for applications in neural repair. Overall, this work underscores the functional importance of AQP4 in both healthy and pathological contexts. The insights gained from studying AQP4’s behaviour and its interaction with biomaterials contribute to foundational knowledge for therapeutic approaches in neural regeneration and glioblastoma treatment, advancing both targeted therapies and biomaterial design.