Physical Chemistry Seminar — Jessica Carder

About the event

Title: Human Aquaporin-4 Orthogonal Array of Particles in Biomimetic Membranes: Aggregation, Protein Tracking and STED:

Abstract: Aquaporin-4 (AQP4) is an integral water channel protein located in the plasma membrane of astrocyte cells in the central nervous system (CNS) and helps to regulate water-ion homeostasis. Some isoforms of AQP4 further order themselves into aggregates known as orthogonal arrays of particles (OAPs). AQP4 exists in two main isoforms, M1 and M23, with M23 being the isoform that favors stabilization by aggregation into OAPs. What role these OAPs play in the membrane of cells is still largely unknown. This study takes these AQP4 aggregates and incorporates them in a supported CNS biomimetic and images them using stimulated emission depletion (STED) super resolution microscopy. Using different ratios of M1 and M23 isoforms, it was found that in the biomimetic system, as the concentration of M1 increased, the smaller the OAPs became. This result is similar to the aggregation behavior seen in native astrocytes. Furthermore, protein tracking studies using total internal reflection (TIRF) microscopy have been used to directly observed interactions between large OAP and individual AQP4 tetramers spontaneously with no outside interactions. This foundational work will lead to future studies exploring AQP4 mechanics under different environmental conditions