Graphene liquid cell electron microscopy for observing early-stage dynamics of amyloids

Abstract

Amyloid protein is one of the target substances causing diverse neurodegenerative disorders, such as Alzheimer’s disease. Recently, the hypothesis that initial and intermediate oligomers cause cellular toxicity has drawn attention. However, understanding formation of amyloids is hampered due to structural polymorphism and complexity of reactions. In addition, assemble-averaged analytic approaches widely adopted has limitations on distinguish detailed molecular process occurred simultaneously. In this dissertation, early-stage dynamic behaviors are revealed by graphene liquid cell electron microscopy. Instability of intermediate fibrillar species is directly observed. To imitate the physiological condition for early-stage of amyloid formation, liquid-flowing graphene chips are developed. By using developed platforms, the dynamic equilibrium growth process is revealed with multimodal analytic approaches. These newly suggested graphene liquid cell platform and techniques are expected to contribute unveiling the diverse molecular processes which are inaccessible with other techniques.