Linear Peptides

Next up in molecular complexity are longer designed peptide surfactants approximately 2–3 nm in length, with a hydrophilic head of one or two charged amino acids and a hydrophobic tail of four or more consecutive hydrophobic ones, e.g. A₆D, V₆D, G₈DD, KV₆. Upon dissolution in water at 4–5 mM, these peptides form a network of cationic or anionic open-ended nanotubes ( fig 3 ) with 30–50 nm diameters and numerous three-way junctions that connect them together; vesicles can fuse or bud out of the nanotubes. The 4–5 nm thick wall is formed by a bilayer of peptides. These tubes are stabilized by hydrophobic effects and they are reminiscent of the nano- and microtubes formed by lipids, but an order of magnitude smaller in diameter. However, unlike conventional surfactants, peptide surfactants pack by hydrogen bonding interactions. In fact, some peptide surfactants display typical β-sheet structure implying a fairly extended backbone. pH is also an important factor since the charge needs to be maintained in the headgoups, to avoid conversion of NTs into large membranous aggregates. Peptide purity is also found to be crucial for the reproducible behavior of peptide NTs.

Fig. 3. (a) Self-assembling nanotubes and vesicles of negatively and positively charged surfactant peptides: (i) V₆D nanotubes; (ii) V₆D vesicles budding out of nanotubes; and (iii) K₂V₆ nanotubes. Color code: green-hydrophobic tails, red-aspartic acid, blue-lysine. (b) Quick-freeze/deep-etch transmission electron micrographs of (i) surfactant peptide nanotubes; (ii) vesicles possibly budding from the nanotubes or vice/versa.

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Alanine (A) and valine (V) produce more homogeneous and stable NTs than glycine (G), isoleucine (I), and leucine (L). For cationic peptides, lysine (K) or histidine (H) are preferred over arginine (R), possibly due to steric effects. Glycine and aspartic acid (D) are also interesting because these amino acids are believed to have been present in the prebiotic environment of the early Earth. If peptides consisting of a combination of these amino acids can form nanotubes and vesicles, they would have the potential to provide primitive enclosures facilitating catalysis and prebiotic molecular evolution. It is also possible to design molecular recognition elements into the peptide, in order to deliver a wide range of substances inside the cell in a site-specific manner. Envisaged applications include carriers for the encapsulation and delivery of a number of small, water-insoluble molecules and large biological molecules, including negatively charged nucleic acids inside the cell, and cosmetic applications.

A biological peptide derived from the amphiphilic core Aβ(16-22) of the Alz peptide can also assemble into parallel β-sheets that produce bilayer structures at low pH (fig 4a). These stack on top of each other in large numbers to give rise to helical ribbons which fuse at the edges to produce highly homogeneous nanotubes (fig 4b) with a 52 nm outer diameter, a 4 nm-thick wall and lengths of several microns. The tubes can be densely coated with negatively charged colloidal Au particles to prevent further NT association. Extensive bundling (diameter of 1 μm and >5 mm contour length) of NTs can be achieved by salting out (fig 4c and 4d). Counter ion mediation allows lateral alignment of the NTs during this process. This is a simple and generic strategy to produce higher order assemblies of homogeneous NTs.

Fig. 4. Proposed model for self-assembly of Aβ(16–22) peptide nanotubes. (a) A flat rectangular bilayer stacks to form a laminate of bilayers. (b) The laminate of bilayers twist to form nanotubes. Cryo-etch high-resolution SEM micrographs of peptide nanotubes: (c) before, and (d) after sulphate bundling.