One dimension, four shapes

Chapter 2 of Peptide Nano-Chemistry and Nanotechnology is about "one-dimensional" peptide nanomaterials. That sounds abstract, but it simply means structures that are long and thin: much longer in one direction than the other two.

The chapter covers four kinds:

  • Nanofibres: long, solid, thread-like structures
  • Nanotubes: hollow cylinders
  • Nanowires: very long fibres, often micrometres in length
  • Nanorods: shorter, stiffer rods

What makes this chapter memorable is how little it can take to build them. In some cases, just two amino acids.

Diphenylalanine: the smallest tube builder

Diphenylalanine, often written FF, is simply two phenylalanines joined together. It is one of the most famous molecules in peptide nanotechnology.

FF happens to be the core recognition motif of the amyloid-beta peptide associated with Alzheimer's disease. When researchers studied it on its own, they found that this tiny dipeptide assembles into remarkably well-ordered, hollow nanotubes. The flat rings on the two phenylalanines stack together, and hydrogen bonds between backbones hold the stacks in place.

The chapter describes how FF nanotubes are made in practice: dissolve FF in a solvent called hexafluoroisopropanol, dilute with water, and the tubes form. It then gives examples of what they have been used for:

  • Drug delivery: FF nanotubes were coupled to folic acid and magnetic nanoparticles as a potential anticancer drug carrier.
  • Drug-releasing coatings: FF nanotubes arranged on a gold surface loaded 98% of an anti-inflammatory drug (flufenamic acid) and released it slowly, suggested as an alternative to polymer coatings for implants.

The chapter also notes nanotubes can have remarkable mechanical properties and interesting electronic and optical behaviour, with potential in optoelectronics.

Rings that stack into tubes

The chapter traces the design of peptide nanotubes back to 1993, when Reza Ghadiri's group made cyclic peptides with alternating left-handed (L) and right-handed (D) amino acids.

Here is why that works. A ring made of alternating D and L amino acids is flat, with all its side chains pointing outward and its backbone hydrogen bonding groups pointing up and down. So the rings stack on top of each other like a pile of washers, bonding to the ring above and below. The result is a hollow tube with a precisely defined inner diameter, set by the size of the ring.

Tubes that cross cell membranes

Because these stacked-ring tubes are hollow, they can act as channels. The chapter describes an oily cyclic peptide, cyclo[Gln-(D-Leu-Trp)4-D-Leu], that forms nanotubes which insert into lipid membranes and create artificial transmembrane channels: tiny pores through which molecules can pass.

Another design went further, placing pH-sensitive chemical groups inside the tube. At low pH, the tubes stayed stable in membranes and let water through but not ions. At higher pH, the groups changed charge, the channel's properties changed, and the tube came apart. A channel that opens and closes depending on acidity.

Nature uses protein channels for exactly this kind of controlled transport. Building one from a small synthetic peptide ring is a striking piece of molecular engineering.

Nanowires from a yeast prion

Nanowires are longer than nanotubes. The chapter describes nanowires built from Sup35, a yeast protein that forms amyloid fibres (it is the protein behind a yeast "prion", a heritable protein state). Researchers attached a tag (biotin) to the protein, and the resulting nanowires could then carry other molecules attached through that tag.

The chapter notes nanowires offer many binding sites along their length, making them useful as templates. Metals or metal oxides can be deposited along the peptide wire, creating metal nanowires for catalysis, electronics and batteries. The peptide acts as a mould and can sometimes be removed afterwards.

Fibres that assemble inside cells

The nanofibre section includes an intriguing study. Researchers designed peptide nanoparticles that could be taken into cells, carrying a light-sensitive sequence. Once inside, shining light on them triggered a subtle shape change, and the peptides reassembled from particles into nanofibres. Those fibres, containing the sequence KLVFF (another amyloid-derived motif), inhibited cell migration and caused cell death.

The clever part is the order of events. Fibres cannot easily get into cells. Particles can. So the researchers sent in particles and built the fibres on site. The chapter describes it as controlling self-assembly in space, without needing chemical reactions.

Metal ions as assembly triggers

The chapter also shows that metal ions can trigger fibre formation:

  • Platinum ions bound to histidines in a hairpin-shaped peptide, driving it to fold and assemble into fibres. Those fibres were then used as templates to grow platinum nanorods with good electrocatalytic activity.
  • Polyoxometalates, large negatively charged metal-oxygen clusters, bound to positively charged peptides and drove them into fibres with enhanced antibacterial activity and better stability.

Why this matters to you

The FF story is a small, beautiful example of how nature's building blocks can do surprising things. A two amino acid fragment of a protein linked to Alzheimer's forms well-ordered tubes in a beaker. Rings of alternating mirror-image amino acids stack into channels. A yeast prion protein becomes a wire.

It also shows that the same behaviours that cause harm in disease, like amyloid fibre formation, can be harnessed deliberately when understood and controlled. Much of this is at the laboratory stage, but it is research worth knowing about, because it is changing what people think peptides can be.

This series explains materials science research for general readers. Most applications described are at the laboratory or animal study stage. Nothing here is medical advice.