Scheme 1. Mechanism of TTR Disassembly and Reassembly Highlighting the Role of Water Molecules in the Process^a.

^aWhen “cold” water molecules (dark blue spheres) that form the tetramer interface are disrupted, tetramers disassemble into dimers and monomers. During reassembly, interactions between the complex and water molecules re-form; however, it must be noted that the water network of the new tetramer may not be the same as the original water network.