Amyloid Assemblies: Protein Legos at a Crossroads in Bottom‐Up Synthetic Biology

One of the major objectives that bottom‐up synthetic biology shares with chemical biology is to engineer extant biological molecules to implement novel functionalities in living systems. Proteins, due to their astonishing structural and functional versatility and to their central roles in the biology of cells, should be cornerstones of synthetic biology. In particular, protein amyloid cross‐β assemblies constitute one of the most stable, conceptually simple and universal macromolecular architectures ever found in Nature and thus have enormous potential to be explored. This article focuses on the concepts behind the use of the amyloid cross‐β‐structural framework as a synthetic biology part, underlining recent basic findings and ideas. The pros and the cons associated with the polymorphism and the cellular toxicity of protein amyloids are also discussed, keeping in mind the possible suitability of these protein assemblies for scaffolding novel orthogonal macromolecular devices in vivo.