Probing protein nanoassemblies in neurodegenerative disease

Atomic force microscopy (AFM) has been utilized in many biological applications and has evolved into a useful tool for structural characterization and for direct measurement of intermolecular forces at the nanoscale level. AFM offers unique advantages compared to other analytical tools, including the ability to perform label-free and fluid phase imaging which allows researchers to visualize, probe, and analyze intricate structures of biological molecules in their native environments. In addition, binding and intermolecular interactions between two biomolecules can be studied using the AFM, making it a very powerful tool for investigating the biomolecular nano-assemblies. This chapter focuses on the application of AFM in neurodegenerative disease studies. We show how AFM can be used to characterize protein structures at various aggregation stages; to detect changes in conformations of proteins and protein-antibody complexes, to determine the binding interactions between an antibody and antigen and to quantify binding specificity of an antibody to its antigen. In addition, we highlight the development of novel AFM techniques to facilitate the study of protein morphologies and interactions in neuroscience research. We hope that this chapter offers new insights and appreciation to the reader on the versatility of the AFM in nanotechnology research, particularly nanobioscience.