Phase Separation Studies of Complexes of Intrinsically Disordered Protein Tau and Anionic Liposomes

Abstract

Tau is a highly soluble intrinsically disordered protein (IDP) characterized classically as a microtubule-associated protein (MAP) in axons of mature neurons. The most well established primary function of tau is to suppress microtubule (MT) dynamic instability providing a stable foundation for organelle trafficking and cell communication. However, the dynamic and polyampholytic nature of tau's peptide composition implies a capacity to interact with charged biological substrates in the cytosol for other distinct functions. There is emerging evidence suggesting that tau associations with charged, specifically anionic, cytosolic molecules may prime pathological structural states seen in neurodegenerative diseases. However, the mechanisms of these secondary interactions are still poorly understood. Therefore, our goal is to understand the structural implications of tau associations with anionic molecules, specifically biological lipid membranes. Here we probe phase transitions of tau-anionic liposomes interactions at different anionic liposome formulations using differential interference contrast microscopy (DIC), fluorescence microscopy, and transmission electron microscopy (TEM).