Invasion and Association of Tethered Collagen Mimetics

University Of Wisconsin Madison, Madison WI

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): Collagen mimetics will be synthesized and investigated for their ability to (1) undergo strand invasion and to (2) self-assemble into fibrils. In the first aim, the idea of strand invasion in protein mimetics will be tested, i.e. whether a single strand of a collagen mimetic triple helix can be displaced by a tighter binding strand to give a thermodynamically more stable helix. In the proposed study, two tight-binding peptide strands and one weak-binding strand (with a known collagen disease mutation) will be tethered together to nucleate triple helix formation. A single tight-binding strand will then be introduced, and monitored for its ability to displace the weak-binding strand in the helix. In the second aim, mimetics with three tethered tight-binding sequences will be evaluated for their ability to self-associate through intermolecular helix formation to provide stable triple helices that approach the length of natural collagen proteins. To favor self-association, the tether will be shifted so that two strands have overhangs in one direction and the third in the opposite direction. This offset will result in sticky ends for intermolecular association. The long-term goal of these studies is to create novel collagen-based biomaterials of defined properties, structure and size. Experimental results have the potential to shed light on the unknown mechanism of collagen fibril formation, and thus may provide methods of treatment for collagen diseases. Generating large networks of synthetic collagen fibers by the interlocking of small molecules via strand invasion or self-association has numerous potential applications in tissue engineering. Synthetic collagens with defined sequences and fibril sizes are also candidates for alternative matrices for human cell culture.