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The self-assembly of nanotubes from chiral amphiphiles and peptide mimics is still poorly understood. Here, we present the first complete path to nanotubes by chiral self-assembly studied with C(12)-β(12) (N-α-lauryl-lysyl-aminolauryl-lysyl-amide), a molecule designed to have unique hybrid architecture. Using the technique of direct-imaging cryo-transmission electron microscopy (cryo-TEM), we show the time-evolution from micelles of C(12)-β(12) to closed nanotubes, passing through several types of one-dimensional (1-D) intermediates such as elongated fibrils, twisted ribbons, and coiled helical ribbons. Scattering and diffraction techniques confirm that the fundamental unit is a monolayer lamella of C(12)-β(12), with the hydrophobic tails in the gel state and β-sheet arrangement. The lamellae are held together by a combination of hydrophobic interactions, and two sets of hydrogen-bonding networks, supporting C(12)-β(12) monomers assembly into fibrils and associating fibrils into ribbons. We further show that neither the "growing width" model nor the "closing pitch" model accurately describe the process of nanotube formation, and both ribbon width and pitch grow with maturation. Additionally, our data exclusively indicate that twisted ribbons are the precursors for coiled ribbons, and the latter structures give rise to nanotubes, and we show chirality is a key requirement for nanotube formation.
Ziserman et al. (Tue,) studied this question.