EAGER: Bone Intrinsic Toughening by Stress Whitening is a Fundamental Molecular Mechanism of Collagen I

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Bone, tendon, ligament, and cartilage carry large forces. The soft parts of the tissues are fibrous molecules (mostly collagens) that are suited for this role. The underlying idea of this research project is that collagen has a molecular-level mechanism that helps these tissues to be strong and tough. A property of normal, tough bone under tension is that it "whitens" just before it breaks. In contrast, brittle bone doesn't whiten noticeably before it breaks. Previous research has shown that whitening results from changes to the collagen molecules in bone. The hypothesis of this EArly-concept Grant For Exploratory Research (EAGER) project is that as these molecules are stretched it results in dehydration that creates strong attachments between the molecules, making them whiter and also postponing breakage. It is theorized that the cause of the dehydration is the same mechanism (called "spinodal decomposition") that is common in polymer solutions, where stretching a solution causes the dissolved polymer to separate into a separate, solid form. The mechanical result is that the fibers in the tissue change from being relatively distributed, flexible, and tough to being dense, stiff, and strong until the tension is released. Whitening is a way to protect the tissue from breaking that, if missing, will result in a brittle bone. Fibrous tissues are found in animals that range from sponges to elephants. Demonstrating existence of an underlying molecular-level, dynamic, mechanical toughening mechanism could help in understanding load support in many animals. It also could explain some bone diseases. If mechanical dehydration explains part of collagen toughness, the knowledge could guide future medical research to make bone tougher as we age. Results of this research will be included in courses on Skeletal Tissue Mechanics and Biomaterials. Whitening was previously attributed to light scattering caused by microcracking in the mineral component of bone, but research from the PI's laboratory has demonstrated that whitening is a property of the collagenous matrix. Review of connective tissue and polymer mechanics literature indicates that the likely mechanism for whitening is tensile stress-induced dehydration of the collagen molecules, referred to as crystallization. This may be caused by extensional strain-dependent spinodal decomposition of the collagen-extracellular fluid solution. There are two research goals. The first is to determine whether stress- and solvent- whitening are dehydration effects. The second is to investigate whether partial dehydration by lateral compression of the collagen fibrils, via non-penetrating osmotic pressure using high molecular weight polyethylene glycol solutions has any of the following effects: a) decreases the strain needed to cause whitening; b) decreases both rupture strain and modulus of rupture (indicating a more brittle tissue); c) increases modulus and ultimate stress; and, finally, d) if the (decreased) strain-to-whitening after compression will predict the same ultimate stress (and other mechanical properties) as for an uncompressed specimen in a solvent of lower Hansen's coefficient that has the same strain-to-whitening. The lateral packing of the collagen molecules and other changes in molecular configuration during mechanical testing of decalcified bone specimens will be monitored using real-time Raman spectroscopy. Raman spectra correlated with lateral molecular packing are expected to show step-wise changes when tension reaches a critical value.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.