Grant: Discovery Grants Program - Individual

Collagen is the protein building block of most mammalian tissues such as tendon, arteries, skin and bone. It is often sourced from various animal tissues and used in a wide array of medical and cosmetic applications such as skin fillers, wound dressing, and guided tissue regeneration. In its crudest extracted form, collagen is the main component of gelatin: a hydrogel used mostly as a food ingredient and as a nonmedicinal ingredient in drugs and nutritional complements. Within our body, collagen forms fibrils, long cables with a diameter in the range of one thousandth of a human hair. Collagen fibrils give our tendons tensile properties comparable to the strongest man-made polymer materials. The assembly of collagen fibrils is a spontaneous process that cells tightly control to achieve a specific structural-mechanical relationship for each tissue. For example, tendons are typically split into two broad classes, the positional ones that are responsible for precise bone positioning such as in the hand, and the energy-storing ones like the Achilles at the heel of the foot that store elastic energy during movement. It is already established that these two types of tendons have different tensile properties. We recently demonstrated, using an atomic force microscopy based approach, that the same dichotomy is true at the collagen fibril level. This unexpected finding offers the opportunity to contrast the structural-mechanical relationships of the two types of fibrils. This is a challenging task that requires sensitive structural probes at the single fibril level compatible with tensile testing techniques at the same scale. To this end, I have assembled a strong team of students and collaborators, and identified three promising techniques: atomic force microscopy for single fibril imaging, spectroscopy and manipulation; nanoscale X-ray diffraction for probing molecular packing at high spatial resolution; and second harmonic generation microscopy for time-resolved studies. We will combine these cutting-edge approaches with theoretical models inspired from soft-matter physics concepts to provide a complete picture of how the structure of collagen fibrils extracted from the two different types of tendon, positional versus energy-storing, changes during stretch and ultimately fails.Our findings will have applications in the biomedical field where novel treatments of tendon injuries, as well as other soft-tissue trauma, could benefit from understanding the molecular nature and determinants of mechanical damage in collagen fibrils. To that end, I already have contacts with the Nova Scotia Tissue Bank to ensure timely translation of the research to clinicians. Another potential area of application is in the design and production of biodegradable, high performance textiles based on proteins.