Synthetic shape-shifting collagen with potential biomedical applications

Synthetic collagen could offer controlled-release drug delivery and tissue engineering

Original source: Materials Today

A shape-shifting nanomaterial that converts from flat sheets to tubes and back again in a controllable fashion has been developed by researchers at Emory University, in collaboration with the Argonne National Laboratory, the Paul Scherrer Institute and the University of Basel. The nanomaterial, made of synthetic collagen, could lead to a range of biomedical applications, including controlled-release drug delivery and tissue engineering.

Naturally occurring collagen is the main structural protein in the connective tissue of the human body, and abundant in our blood vessels, gut and muscles. Synthetic collagens are intrinsically biocompatible and structurally similar to native collagen proteins, while synthetic peptides improve upon conventional organic polymers in sequence control at the nanoscale, enabling better control over the self-assembly process.

The laboratory of Vincent Conticello has been exploring the development of synthetic collagen nanosheets suitable for applications in biomedicine and other complex technologies for many years. However, as detailed in the Journal of the American Chemical Society [Merg et al. J. Am. Chem. Soc. (2020) DOI: 10.1021/jacs.0c08174], here the team were able to convert the nanomaterial from sheets to tubes and back again just by varying the pH in its environment.

Their discovery that synthetic collagen peptides could self-assemble into crystalline nanosheets was fortuitous, as they were trying to fabricate synthetic collagen fibers for tissue engineering, but the peptides showed a preference for 2D rather than 1D assembly, with the initial designs resulting in nanosheets with identical upper and lower surfaces. However, it is more useful for the two surfaces to be chemically distinguishable for integration with medical devices, with one surface compatible with the device and the other with functional proteins in the body. They therefore re-designed the peptide sequences to promote self-assembly into nanosheets displaying non-identical surfaces.

Engineering these surfaces into single collagen sheets resulted in the sheets curling up. It was shown that this shape-shifting transition was reversible, and it was possible to control if a sheet was flat or curled by changing the pH of the solution it was in. This helped to tune the sheets to shape shift at particular pH levels in controllable way at the molecular level through design. As Conticello and researcher Andrea Merg told Materials Today, “We have demonstrated that we can create different collagen architectures, such as tubes and sheets, that are not observed in nature and trigger the interconversion between them”.

Achieving such controllable structural transitions could be extended to polymer crystals or other 2D materials, as these synthetic peptides offer proof-of-principle. The team are now investigating whether potential guests, such as small molecules, peptides, proteins and nucleic acids, could trigger the transitions and be confined within the scrolled layers of the tubes, while mineralized nanocomposites could also be a possibility for synthetic bone through controlling the surface chemistry of the assemblies.