Turning peptides into gold

A possible answer to this quest came from a rather  unexpected source: the SARS-CoV-2 virus. A team of researchers from Spain, the UK and the ILL discovered that two peptides, FP1 and FP2, crucial for viral fusion to host cell membranes, display remarkable self-assembling properties. These peptides, identified as putative fusion peptides, are located at the N-terminus of the S2' subunit of the spike protein.

"First, we showed that the peptides were indeed able to self-assembly at the interface between water and air", says Armando Maestro, who coordinated the study. A molecular characterisation of the structures revealed that they consisted of stacks of tiny molecular sheets made of FP1 and FP2. Interestingly, the structures formed by FP1 and FP2 had different morphological properties: while FP1 formed rather straight and rigid fibers, FP2 led to more flexible, curved ones which eventually assembled into spiral-like structures. Remarkably, the curvature of the fibers could be controlled by varying the compression forces exerted on them.

"After this initial success, we were really interested in seeing how FP2 peptide structures developed at the air-liquid interface in real time", explains Alberto Alvarez-Fernandez, the first author of the team's publication. "We chose neutron reflectometry as our main method since neutrons can detect even subtle changes of an interface as molecular layers are deposited on it." The FP2 layers were determined to be laterally homogenous and were best described by a two-layer model with one peptide layer in contact with water and the other one with air. With increasing surface pressure, the thickness of the film increased, indicating that the layer extended into the liquid phase.

In a final step, the team produced gold replicas of the peptide spirals by immersing them into an aqueous gold solution and treating them with a combination of ultraviolet light and ozone. "The advantage of this method is that the resulting gold spirals are very uniform. It is also extremely reproducible and versatile since it can be extended to other inorganic materials", says Armando Maestro.

Using a multi-technique and interdisciplinary approach including neutrons, this study therefore provides a deeper understanding of peptide self-assembly. In addition, it opens the door towards an exciting variety of manufacturing processes of functional nanomaterials.