Self-assembled structures formed by fatty-acid-modified elastin-like polypeptides (FAME). Researchers use temperature cues to make the molecules assemble themselves. (Credit: Davoud Mozhdehi and Kelli Luginbuhl)

Biomedical engineers have demonstrated a new approach to making self-assembled biomaterials that relies on protein modifications and temperature. The hybrid approach allows researchers to control self-assembly more precisely, which may prove useful for a variety of biomedical applications from drug delivery to wound healing.

Biomaterials have broad applications across the fields of tissue engineering, regenerative medicine and drug delivery. Protein- and peptide-based materials are attractive for these applications because they are non-toxic, biodegradable and have a well-defined composition. But these biomaterials are limited to the 20 amino acids found in nature.

One strategy to expand the chemical diversity of protein-based materials is post-translational modification (PTM), a powerful set of reactions that nature uses to chemically transform proteins after they are synthesized from genes. PTM can modify specific amino acids in proteins or add non-protein structures, such as sugars and fatty acids. To make such a hybrid material with useful biomedical properties, researchers focused on creating a series of lipid-modified polypeptides, also called fatty-acid-modified elastin-like polypeptides, or FAMEs.

When a lipid is fused to a peptide sequence, the different physical properties of the lipid and peptide result in the formation peptide amphiphiles, or PAs. Typical PAs can self-assemble into diverse structures like long fibers, making them useful as scaffolds for tissue engineering. However, this happens spontaneously and these materials cannot be injected into the body but instead have to be implanted. The research team added another useful biomaterial, elastin-like polypeptide (ELP), because it can change from a soluble state to an insoluble state, or vice-versa, depending on temperature.

Using three components — a lipid myristoyl group‚ a beta-sheet-forming peptide sequence, and an elastin-like polypeptide (ELP) — the researchers created a hybrid biomaterial, the FAME polypeptide, that changes from molecules floating in solution into a solid material, simply by raising the temperature.

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