Professor Yujia Xu of Hunter College-CUNY is supported by the Macromolecular, Supramolecular, and Nanochemistry (MSN) Program in the Division of Chemistry to investigate the mechanisms of self-assembly of the collagen triple helix, and to use collagen fibers in nanomaterial design. The specific aims are to investigate the factors that control the autonomous unfolding of segments of the triple helix and to determine how these microunfolding processes affect the self-assembly of the triple helix.
Understanding the mechanisms of self-assembly of collagen is important from fundamental and applied points of view. The knowledge gained will inspire and inform the design of different complex protein structures, biomimetic materials and scaffolds. Students will be exposed to research at the interface of chemistry and biology, and the research results will be integrated into course material at Hunter College which serves a diverse student population.
Collagen is the most abundant protein in humans and also the major component of the connective tissues. The proper functioning of collagen is directly linked to the strength of the bones, the elasticity of the skin and blood vessel walls, the clarity of the cornea of the eye and the smooth working of the joints, to name just a few. Collagen also represents one of the most prevalent cases where the diverse biological functions of a biomolecule are derived from the ability of the self-assembly of simpler molecular units into large molecular complexes. The major functional forms of collagen are long fibrils with distinctive axially repeating structure features, also known as the D-periodic fibrils. The fibrillogenesis of collagen includes the self-assembly of the molecular units of collagen – the collagen triple helix. However, the molecular mechanism of this important biological process remains unknown despite extensive study. During the funding period of this grant, we have, for the first time, created a collagen-like fibrils via the self-assembly of a designed triple helical peptide. More specifically, our initial stage of the work indicated that the ‘code’ for collagen fibril assembly lies within the repeating patterns of identical amino acid sequences. The triple helical peptide we designed consists of three tandem repeats of identical amino acid sequences. The size of the repeating units of the sequences is directly linked to the axially repeating features of the self-assembled fibrils. Further, this designed peptide containing neither hydroxyproline nor telopeptides, two factors thought necessary for collagen self-assembly; the fibril assembly of this peptide, thus, establishes minimal requirements for fibril formation and accentuates the critical role sequence periodicity plays. As it has been demonstrated throughout the history of protein chemistry and biochemistry, the ability to mimic a biological phenomenon using model molecules often opens the doors for an in-depth understanding of the biological processes and leads to the development of new biomaterials for a diverse range of applications. This novel development of D-periodic collagen fibril supplies a unique model for understanding the fibrillogenesis of collagen and for advancing the field of protein design. In the ongoing research we are using the knowledge gained from this funded project to further define molecular interactions that are critical for the functions of collagen and to design new nano-materials using collagen as a molecular scaffold for applications such as bio-imaging, radiotherapy and nano-scale electronic circus. The funding led to three presentations in research conferences and several manuscripts (One submitted, two in preparation). The funding also supported the training of three undergraduate students, two master degree students, two Ph.D. students and one postdoctoral fellow on conducting original research.
