Nanodisc-to-Nanofiber Transition of Noncovalent Peptide–Phospholipid Assemblies

We report a novel molecular architecture of peptide–phospholipid coassemblies. The amphiphilic peptide Ac-18A-NH2 (18A), which was designed to mimic apolipoprotein α-helices, has been shown to form nanodisc structures with phospholipid bilayers. We show that an 18A peptide cysteine substitution at residue 11, 18A[A11C], forms fibrous assemblies with 1-palmitoyl-2-oleoyl-phosphatidylcholine at a lipid-to-peptide (L/P) molar ratio of 1, a fiber diameter of 10–20 nm, and a length of more than 1 μm. Furthermore, 18A[A11C] can form nanodiscs with these lipid bilayers at L/P ratios of 4–6. The peptide adopts α-helical structures in both the nanodisc and nanofiber assemblies, although the α-helical bundle structures were evident only in the nanofibers, and the phospholipids of the nanofibers were not lamellar. Fluorescence spectroscopic analysis revealed that the peptide and lipid molecules in the nanofibers exhibited different solvent accessibility and hydrophobicity from those of the nanodiscs. Furthermore, th...