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

骨、肌腱、韧带和软骨承受很大的力。组织的柔软部分是纤维分子（主要是胶原蛋白），适合这个角色。这个研究项目的基本思想是胶原蛋白具有一种分子水平的机制，可以帮助这些组织变得强壮和坚韧。正常、坚韧的骨头在受到拉伸时的一个特性是，它在断裂之前会变白。相比之下，脆性骨在断裂之前不会明显变白。先前的研究表明，骨骼中的胶原蛋白分子发生了变化，从而导致了美白。这个早期概念探索性研究资助（EAGER）项目的假设是，当这些分子被拉伸时，它会导致脱水，从而在分子之间产生牢固的附着物，使它们更白，也推迟了断裂。从理论上讲，脱水的原因与聚合物溶液中常见的机制（称为“spinodal分解”）相同，拉伸溶液会导致溶解的聚合物分离成单独的固体形式。其力学结果是组织中的纤维由相对分布、柔韧、坚韧转变为致密、坚硬、坚固，直至张力释放。美白是一种保护组织不被破坏的方法，如果失去这种组织，就会导致骨质脆性。纤维组织存在于从海绵到大象的动物中。证明存在潜在的分子水平，动态，机械增韧机制可以帮助理解许多动物的负载支持。这也可以解释一些骨骼疾病。如果机械脱水解释了胶原蛋白韧性的部分原因，那么这一知识可以指导未来的医学研究，使骨骼随着年龄的增长而变得更坚硬。这项研究的结果将包括在骨骼组织力学和生物材料课程中。此前，美白被认为是由骨骼矿物质成分微开裂引起的光散射造成的，但PI实验室的研究表明，美白是胶原基质的一种特性。对结缔组织和聚合物力学文献的回顾表明，美白的可能机制是胶原蛋白分子的拉伸应力引起的脱水，即结晶。这可能是由于胶原-细胞外液溶液的拉伸应变依赖性独立分解引起的。有两个研究目标。首先是确定应力增白和溶剂增白是否都是脱水作用。其次是研究是否通过使用高分子量聚乙二醇溶液通过非渗透压对胶原原纤维进行侧压的部分脱水具有以下任何效果：a)减少引起美白所需的张力；B)断裂应变和断裂模量均降低（表明组织更脆）；C)增加模量和极限应力；最后，d)压缩后（减小的）应变-白变是否与未压缩试样在具有相同应变-白变的较低汉森系数的溶剂中预测相同的极限应力（和其他力学性能）。在脱钙骨标本的力学测试过程中，胶原蛋白分子的横向堆积和其他分子结构的变化将使用实时拉曼光谱进行监测。当张力达到临界值时，与横向分子堆积相关的拉曼光谱预计会呈现阶梯变化。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.