Exploration of the hierarchical assembly space of collagen-like peptides beyond the triple helix
Le Yu, Mark A. B. Kreutzberger, Thi H. Bui, Maria C. Hancu, Adam C. Farsheed, Edward H. Egelman, Jeffrey D. Hartgerink
Abstract
The de novo design of self-assembling peptides has garnered significant attention in scientific research. While alpha-helical assemblies have been extensively studied, exploration of polyproline type II helices, such as those found in collagen, remains relatively limited. In this study, we focus on understanding the sequence-structure relationship in hierarchical assemblies of collagen-like peptides, using defense collagen Surfactant Protein A as a model. By dissecting the sequence derived from Surfactant Protein A and synthesizing short collagen-like peptides, we successfully construct a discrete bundle of hollow triple helices. Amino acid substitution studies pinpoint hydrophobic and charged residues that are critical for oligomer formation. These insights guide the de novo design of collagen-like peptides, resulting in the formation of diverse quaternary structures, including discrete and heterogenous bundled oligomers, two-dimensional nanosheets, and pH-responsive nanoribbons. Our study represents a significant advancement in the understanding and harnessing of collagen higher-order assemblies beyond the triple helix. Despite advances in machine learning approaches, de novo design of collagen-based materials remains difficult. In this study, based on the natural structure of the defense collagen family of proteins, designed triple helical peptide assemblies are found to form ribbons and a variety of bundled, porous architectures.