Molecular Insight into the β‑Sheet Twist\nand Related Morphology of Self-Assembled Peptide Amphiphile Ribbons

Abstract

Self-assembly\nof high-aspect-ratio filaments containing β-sheets\nhas attracted much attention due to potential use in bioengineering\nand biomedicine. However, precisely predicting the assembled morphologies\nremains a grand challenge because of insufficient understanding of\nthe self-assembly process. We employed an atomistic model to study\nthe self-assembly of peptide amphiphiles (PAs) containing valine–glutamic\nacid (VE) dimeric repeats. By changing of the sequence length, the\nassembly morphology changes from flat ribbon to left-handed twisted\nribbon, implying a relationship between β-sheet twist and strength\nof interstrand hydrogen bonds. The calculations are used to quantify\nthis relationship including both magnitude and sign of the ribbon\ntwist angle. Interestingly, a change in chirality is observed when\nwe introduce the RGD epitope into the C-terminal of VE repeats, suggesting\narginine and glycine’s role in suppressing right-handed β-sheet\nformation. This study provides insight into the relationship between\nβ-sheet twist and self-assembled nanostructures including a\npossible design rule for PA self-assembly.