Biomedical engineers have demonstrated that, by injecting an artificial protein made from a solution of ordered and disordered segments, to solid scaffold forms in response to body heat, and in a few weeks seamlessly integrated into tissue.
The ability to combine these segments into proteins with unique properties will allow researchers to precisely control the properties of new biomaterials for applications in tissue engineering and regenerative medicine . The study was published in the journal Nature Materials.
Proteins function by folding , origami-like, and interacting with specific biomolecular structures. Researchers previously thought that proteins needed a fixed shape, but over the last two decades, there has been a growing interest in intrinsically disordered proteins (IDPs).
Amino Acid Sequences
Unlike their well-folded counterparts, IDPs can adopt a plethora of distinct structures. However, these structural preferences are non-random, and recent advances have shown that there are well-defined rules that connect information in the amino acid sequences of IDPs to the collections of structures they can adopt.
Researchers have hypothesized that versatility in protein function is achievable by stringing together with well-folded proteins with IDPs-rather like pearl necklaces. This versatility isobvious in biological materials like muscle and silk fibers, which are made of proteins that combine ordered and disordered regions, enabling the materials to exhibit characteristics like the elasticity of rubber and the mechanical strength of steel.
Due to the challenges of using elastin itself, the research team worked with elastin-like polypeptides (ELPs), which are fully disordered proteins made to mimic pieces of elastin. ELPs are useful biomaterials because they can undergo phase-changes from a soluble to an insoluble state.
While this makes these materials useful for applications like long-term drug delivery, their liquid-like behavior prevents them from being effective scaffolds for tissue engineering applications.
"Frankenstein" proteins that combine ordered domains and disordered regions leading to so-called incomplete proteins (POPs), which is equipped with the structural stability of ordered proteins without losing the ELPs ability to become liquid or solid via temperature changes.
Designed as a fluid at room temperature that solidifies at body temperature, these new biomaterials form stable, porous scaffold when injected that rapidly integrates into the surrounding tissue with minimal inflammation and promotes the formation of blood vessels.
Moving ahead, the team hopes to study the material in animal models to examine potential uses in tissue engineering and wound healing and to develop a better understanding of why the material promotes vascularization. If these studies are effective, Roberts is optimistic that the new material could become the basis for a biotech company.
They also want to develop a deeper understanding of the interactions between the ordered and disordered portions in these versatile materials. We've been so fascinated with the phase behavior derived from the disordered domains that we neglected the properties of the ordered domains, which turned out to be quite important.
By combining ordered segments with disordered segments there is a whole new world of materials we can create with beautiful internal structure without losing the phase behavior of the disordered segment, and that's exciting.