title: Elucidation of the self-assembly pathway of lanreotide octapeptide into beta-sheet nanotubes: role of two stable intermediates.
abstract: Nanofabrication by molecular self-assembly involves the design of molecules and self-assembly strategies so that shape and chemical complementarities drive the units to organize spontaneously into the desired structures. The power of self-assembly makes it the ubiquitous strategy of living organized matter and provides a powerful tool to chemists. However, a challenging issue in the self-assembly of complex supramolecular structures is to understand how kinetically efficient pathways emerge from the multitude of possible transition states and routes. Unfortunately, very few systems provide an intelligible structure and formation mechanism on which new models can be developed. Here, we elucidate the molecular and supramolecular self-assembly mechanism of synthetic octapeptide into nanotubes in equilibrium conditions. Their complex hierarchical self-assembly has recently been described at the mesoscopic level, and we show now that this system uniquely exhibits three assembly stages and three intermediates: (i) a peptide dimer is evidenced by both analytical centrifugation and NMR translational diffusion experiments; (ii) an open ribbon and (iii) an unstable helical ribbon are both visualized by transmission electron microscopy and characterized by small angle X-ray scattering. Interestingly, the structural features of two stable intermediates are related to the final nanotube organization as they set, respectively, the nanotube wall thickness and the final wall curvature radius. We propose that a specific self-assembly pathway is selected by the existence of such preorganized and stable intermediates so that a unique final molecular organization is kinetically favored. Our findings suggests that the rational design of oligopeptides can encode both molecular- and macro-scale morphological characteristics of their higher-order assemblies, thus opening the way to ultrahigh resolution peptide scaffold engineering.
authors.affiliation: Institut de Physique de Rennes, UMR 6251 CNRS & Universite Rennes 1, 263 Avenue du general Leclerc, F-35042 Rennes Cedex, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Pouget
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fay
authors.forename: Erik
authors.initials: E
authors.lastname: Dujardin
authors.forename: Nadège
authors.initials: N
authors.lastname: Jamin
authors.forename: Patrick
authors.initials: P
authors.lastname: Berthault
authors.forename: Lionel
authors.initials: L
authors.lastname: Perrin
authors.forename: Anjali
authors.initials: A
authors.lastname: Pandit
authors.forename: Thierry
authors.initials: T
authors.lastname: Rose
authors.forename: Céline
authors.initials: C
authors.lastname: Valéry
authors.forename: Daniel
authors.initials: D
authors.lastname: Thomas
authors.forename: Maïté
authors.initials: M
authors.lastname: Paternostre
authors.forename: Franck
authors.initials: F
authors.lastname: Artzner
mesh_terms: D000595:Amino Acid Sequence; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D043942:Nanotubes / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012822:Silicon Dioxide / Q000737:chemistry; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000737:chemistry; D013499:Surface Properties
chemical_list: D010455:Peptides; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin; D012822:Silicon Dioxide