Context dependence in assembly code for supramolecular peptide materials and systems

Abstract

Living systems provide the most sophisticated materials known. These materials are created from a few dozen building blocks that are driven to self-organize by covalent and non-covalent interactions. Biology’s building blocks can be repurposed for the design of synthetic materials that life has not explored. In this Review, we examine the bottom-up design, discovery and evolution of self-assembling peptides by considering the entire supramolecular interaction space available to their constituent amino acids. Our approach focuses on sequence context, or how peptide sequence and environmental conditions collectively influence peptide self-assembly outcomes. We discuss examples of peptides that assemble through multimodal backbone, side chain and water interactions. We conclude that a more systematic (comparing sequences side-by-side), integrated (pairing computation and experiment) and holistic (considering peptide, solvent and environment) approach is required to better understand and fully exploit amino acids as a universal assembly code. This goal is particularly timely, because laboratory automation and artificial intelligence now have the potential to accelerate discoveries in these highly modular and complex materials, beyond the limited sequence space that biology uses.