Naturally Fibrous Mimic

One of the important components of the extracellular matrix is collagen, which comprises the major structural protein component of higher organisms. However, it remains a major challenge to emulate the unique structural and biological properties of native collagenous biomaterials in synthetic analogues. Consequently, numerous opportunities exist for synthetic collagens in biomedical applications as extracellular matrix analogues, if the appropriate materials could be constructed that retain and expand upon the desirable properties of native collagen fibrils.

The exploration of chemical and molecular genetic techniques to design and synthesize collagen-mimetic polypeptides and fibers that are competent for self-assembly into structurally defined protein fibrils is an intriguing avenue for exploration. In this context, Shyam Rele and colleagues have been leading the efforts in the de novo design of nanostructured biological materials through self-assembly of peptides and proteins.

Rele, together with Elliot Chaikof and Vince Conticello in the Laboratory of Bio/Molecular Engineering and Advanced Vascular Technologies at Emory University School of Medicine have been successful in designing and synthesizing the first ever Synthetic Collagen Peptide system which is a 36 amino acid long unit which self-assembles into a fibrous structure with well-defined periodicity reminiscent of native collagen observed in the human body.

Specifically, the synthesized peptide protomer which is made up of three heterotrimeric peptide repeat units contains a hydrophobic proline-hydroxyproline-glycine core flanked on both the sides by distinct sets of peptide repeats containing either negatively (Glutamic acid) or positively (Arginine) charged amino acid residues. When positioned appropriately, these charged amino acids bias and adopt the triple helical self-assembly which undergoes fibrillogenesis at physiological temperatures producing D-periodic microfibers driven through electrostatic interactions.

Transmission electron microscopy on annealed samples revealed that fiber growth proceeded within several hours by initial formation of smooth fibrils that were hundreds of nanometers in length and tens of nanometers in diameter. These fibrils displayed tapered tips similar to the tactoidal ends of native collagen fibers from which continued fiber growth is thought to occur. The D-periodicity of the synthetic collagen-mimetic microfibers was approximately 18 nm. Significantly, the collagen mimic shows a high propensity for self-association following a nucleation-growth mechanism even at lower concentrations (<1.0 mg/mL) and neutral pH. This following discovery for making human collagen in the laboratory is pathbreaking in the field of nanotechnology and bio-inspired biomaterials. Several scientists for the past three decades have been trying to synthesize and emulate collagen's remarkable properties and have failed in their attempts to mimic the long, fibrous molecules found in nature. The ability of Rele, Chaikof and Conticello to generate a synthetic collagen in a laboratory (in vitro) on a nanomolecular level for the first time, therefore represents an important milestone in nanotechnology and biomaterial development. Such self-assembling peptides may have broad applications in medicine, neurodegenerative diseases, protein folding catalyst design, bio-nanotechnology, tissue engineering and origins of life research. Furthermore, generation of such nanostructured molecules which mimic native structural proteins will lay the future ground work for unraveling complex phenomena including collagen fiber formation in protein conformational diseases and for the design of new materials with biological, chemical, and mechanical properties that exceed those of currently available synthetic polymers.

The propensity to generate such self-assembling, biologically compatible peptide scaffolds to arrange themselves into fibers, tubules, and a variety of geometrical layers, establishes an important substrates for cell growth, differentiation, and biological function, and will have an important impact in the treatment of cardiovascular, orthopedic, and neurological disease.

Adapted from a write-up supplied by Rele. Further details can be found in JACS, vol 129, 14780-14787.

Author: spinneret

This post originally appeared in full in David Bradley's hosted Spinneret blog (geddit?). Hopefully, any molecular structures and links are hooking up to the Chemspider database correctly, please let us know if you have problems with mol files, InChI code etc