Self-Assembled Collagen Networks of Predictable Topologies

University Of Vermont & State Agricultural College, Burlington VT

Investigators

Abstract

ID: MPS/DMR/BMAT(7623) 0907599 PI: Case, Martin ORG: University of Vermont Title: Self-Assembled Collagen Networks of Predictable Topologies INTELLECTUAL MERIT: Fibrous collagen is the most abundant mammalian protein. Fibers of collagen are processed in situ as they form in vivo, and this processing introduces irreversible changes that cannot be undone by any physical or chemical extraction process. Consequently, a synthetic analog is extremely desirable as a route to obtaining useful quantities of this versatile protein for materials or therapeutic applications. This proposal presents a biologically inspired approach whereby collagen triple helices self-assemble and are then guided to fibrillar oligomerization. The key process is an energetically coupled stabilization of the triple helix with concomitant setting of the staggered polypeptide register. The approach uses metal-directed assembly to form two fundamental structures: capping trimers and propagating trimers. The capping trimers are aligned by metal complex formation at either the N-terminal or the C-terminal ends (N-cap and C-cap, respectively). They present "sticky" connections at the other end, in which the terminal residues are offset from each other. The propagating trimers are assembled by metal complexation in the middle of the sequence, and present staggered sequences at either end that are complementary to the N/C caps. Binding of the N-cap and C-cap trimers to the appropriate ends of the propagating species, rather than forming an N-Cap/C-Cap dimer, is driven by electrostatic complementarity. It is possible consequently to access much larger procollagen subunits than has hitherto been possible, and the assembly process itself is subject to a much higher degree of control. BROADER IMPACTS: There is currently no practical route to a synthetic collagen, and success in the proposed research could have far reaching benefits for many aspects of regenerative medicine. The PI has collaborations with the College of Medicine at the University of Vermont (UVM) with groups working on spinal reconstruction and blood clotting, both of which activities would benefit from the availability of synthetic collagen. The project will support the work of one graduate student in a highly interdisciplinary environment as well as 4 - 5 undergraduates per year. Funds are budgeted for support of the undergraduate research students. As a participant in Project SEED of the American Chemical Society, the PI will provide opportunities for economically disadvantaged high school students to participate in a meaningful research project in his laboratory during the summer months.