Amyloid fibrils nucleated and organized by DNA origami constructions

Amyloid fibrils are ordered, insoluble protein aggregates that are associated with neurodegenerative conditions such as Alzheimer’s disease(1). The fibrils have a common rod-like core structure, formed from an elongated stack of β-strands, and have a rigidity similar to silk (Young’s modulus of 0.2-14 Gpa)(2). They also exhibit high thermal and chemical stability(3), and can be assembled in vitro from short synthetic non-disease-related peptides(4,5). As a result, they are of significant interest in the development of self-assembled materials for bionanotechnology applications(6). Synthetic DNA molecules have previously been used to form intricate structures and organize other materials such as metal nanoparticles(7,8), and could in principle be used to nucleate and organize amyloid fibrils. Here we show that DNA origami nanotubes can sheathe amyloid fibrils formed within them. The fibrils are built by modifying the synthetic peptide fragment corresponding to residues 105-115 of the amyloidogenic protein transthyretin (TTR)(9), and a DNA origami(10) construct is used to form 20-helix DNA nanotubes with sufficient space for the fibrils inside. Once formed, the fibril-filled nanotubes can be organized onto predefined two-dimensional platforms via DNA-DNA hybridization interactions.