Multi-scale Characteristics of Bone Toughness

骨骼既结实又坚韧，因为它独特的成分和结构。骨骼由两个主要组成部分组成：一种硬矿物和一种软蛋白质。这些构建块以不同的方式组织起来，从分子水平到整个骨骼水平，形成了一个分层的复合材料。构建块的组成或组织的变化会导致骨骼变得脆弱或脆弱，但具体发生的方式尚不清楚。我们研究的目的是了解不同层次的变化如何影响骨骼的强度和韧性。所获得的见解将有助于定义骨骼韧性的关键特征，从中我们可以确定骨骼在衰老和疾病中失败的原因。在这个项目的范围内，我们将通过1)成人社区教育外展研讨会，2)让高中生暑期学生参与研究，以及3)开发一个关于事物为什么断裂的小学科学模块，将骨骼和材料研究的兴奋带给公众。本研究的目的是在全骨(Mm)、组织(微米)、纤维(Nm)和分子(Angstrom)长度尺度上确定骨骼的结构、成分和力学性能。我们将检查与野生型小鼠相比，具有改变蛋白质(转基因、基因突变和基因敲除模型)的各种小鼠品系。被改变的蛋白质可能是构成成分本身(如脆性骨病中的胶原缺陷)，也可能是影响骨骼强度和韧性的组织和矿化过程所必需的蛋白质(如交联蛋白)。在整个骨骼水平上，我们将从缺口三点弯曲中确定表征起始和扩展韧性的阻力曲线。在组织层面，我们将用定量背向散射扫描电子显微镜检测矿物质密度，并绘制弹性模数图，以确定材料特性的异质性。在纤维水平，我们将用动态力学分析来研究未矿化的胶原(来自同一小鼠的尾腱)的力学性能，并用小角X射线散射来研究矿化的胶原纤维。在分子水平上，我们将测量交联蛋白和非胶原蛋白。这种对机械、结构和成分特性的多尺度分析将确定影响骨骼强度和韧性的因素。

Bone is both strong and tough because of its unique composition and structure. Bone is composed of two main building blocks: a hard mineral and a soft protein. These building blocks are organized in distinct ways from the molecular level up to the whole bone level, forming a hierarchical composite. Alterations of the composition or organization of the building blocks results in bones that are weak or brittle, but the specific way this happens is not known. The objective of our research is to understand how alterations across levels of hierarchy affect the strength and toughness of bone. The insights gained will help define the critical characteristics of bone toughness, from which we can determine why bone fails in aging and disease. In the scope of this project we will bring the excitement of bones and materials research to the public through 1) adult community education outreach seminars, 2) involving high school summer students in the research, and 3) developing an elementary school science module on "why things break." The objective of this research is to determine the structural, compositional, and mechanical properties of bones at the whole bone (mm), tissue (micron), fibril (nm), and molecular (Angstrom) length scales. We will examine various mouse strains that have altered proteins (transgenic, genetic mutations, and knock-out models) compared to wild type mice. The altered proteins may be the building blocks themselves (such as collagen defects in brittle bone disease) or proteins that are essential to organization and mineralization processes (such as crosslinking proteins) that affect strength and toughness of the bone. At the whole bone level we will determine resistance curves, which characterize both initiation and propagation toughness, from notched 3-point bending. At the tissue level we will examine mineral density with quantitative backscatter scanning electron microscopy and map the elastic modulus to define heterogeneity of material properties. At the fibril level we will examine the mechanics of unmineralized collagen (from tail tendon of the same mice) with dynamic mechanical analysis and mineralized collagen fibrils with small angle x-ray scattering. At the molecular level we will measure crosslinking and non-collagenous proteins. This multi-scale analysis of mechanical, structural, and compositional properties will identify the factors contributing to bone strength and toughness.