KCS

Undesirable aggregation of intrinsically disordered proteins including tau protein and α-synuclein causes progressive death of neuronal cells as neurodegenerative diseases including Alzheimer’s and Parkinson’s disease. The protein aggregation in cells and tissues is known to be promoted by oxidative stress under acidic conditions and affects the integrity of organellular and cellular membranes. However, the complex nature of physiological environments has hampered the deep investigation of the effect of the protein aggregation to the membranes causing propagative cell death. Recently, cell-like artificial microcompartments have been intensively investigated as protocells (or artificial cells) for better interrogating and understanding of cellular functions and behaviors of interest in a simplified form. A rational organization of chemical and biological components in a compartment allowed the construction of protocells mimicking important cellular functions and behaviors under a well-defined and controllable condition. Until recently, little effort has been devoted to construct a protocell that mimics destabilization of biological membranes by protein aggregation despite its heavy involvement in neurodegenerative diseases. In this talk, I will present our recent efforts to provide a giant unilamellar vesicle as a protocell mimicking destabilization of biological membranes by intracellular protein aggregation in a controllable manner. In addition, the intra- and intercellular effects of the protein aggregation to organelle and other cell mimics in a simplified system will be discussed.