Water vs. mineral-collagen interaction in bone

描述(申请人提供)：骨骼骨折是老年人的主要保健问题，由于骨骼质量恶化，这取决于骨成分(即矿物质、胶原蛋白和水)的性质和空间排列。其中，水主要以三种形式分布在骨骼中：流动水(在毛孔中)、松散结合水(附着在矿物和胶原表面)和紧密结合水(作为矿物和胶原分子的一部分)。众所周知，骨的脱水会显著降低组织的韧性，这表明水与其他骨成分(即矿物质和胶原)的相互作用对骨的韧性起着重要作用。与临床相关的是，最近的研究结果表明，水的增韧作用随着年龄的增长而减弱，这表明与年龄相关的变化可能以某种方式阻止了水在骨骼中作为塑化剂的作用(S)。一般来说，水分子可以通过两种主要方式与矿物和胶原蛋白相互作用：极性相互作用(范德华力)和更强的氢键。因此，了解水与矿物质和胶原蛋白之间的相互作用(极性相互作用和氢键)如何参与骨组织的增韧是很重要的。以前的证据表明，水与矿物质和胶原蛋白之间的相互作用可以对骨的力学行为产生重大影响。为此，我们建议采用一种新的实验设计和最先进的技术来研究水的极性相互作用和氢键能力对骨的力学行为的贡献。这样的理解将有助于破译水在维持骨骼韧性中的作用，并进一步有助于理解与年龄相关的骨超微结构变化，这些变化阻碍了水对组织韧性的贡献。本研究的假设是，水分子通过极性相互作用和氢键作用影响矿物和胶原之间的相互作用，从而对骨骼的韧性产生显著影响。为了验证这一假说，将解决两个具体目标：1)确定水分子的极性(Van Der Waals)力和氢键能力对矿物和胶原蛋白之间相互作用的影响；以及2)确定水分子的极性(Van Der Waals)相互作用和氢键能力对骨骼力学行为的影响。结合目标1和目标2的结果，将阐明水在维持骨骼韧性方面的作用。 与公共健康相关：先前的证据表明，水在维持骨骼韧性方面的作用随着年龄的增长而减弱。利用最先进的技术进行系统的研究，从超微结构水平上阐明水对骨的增韧机理。这样的理解将有助于阐明与年龄相关的骨超微结构的变化及其与年龄相关的骨折的相关性。

DESCRIPTION (provided by applicant): Skeletal fractures are a major health care concern of elderly populations due to deteriorated bone quality, which is dependent on the properties and spatial arrangement of bone constituents (i.e., mineral, collagen and water). Among them, water has been identified to distribute in bone in three major forms: mobile water (in pores), loosely bound water (attached to mineral and collagen surfaces), and tightly bound water (as part of mineral and collagen molecules). It has been well known that dehydration of bone significantly reduces the toughness of the tissue, suggesting that interactions of water with the other bone constituents (i.e., mineral and collagen) play a significant role in bone toughness. Relevant to clinical concerns, recent findings indicate that the toughening effect of water diminishes with aging, suggesting that age-related changes may somehow block the pathway(s) for water to function as a plasticizer in bone. In general, water molecules may interact with mineral and collagen phases in two major ways: polar interactions (van der Waals forces) and much stronger hydrogen bonds. Thus, it is important to understand how such interactions (polar interaction and hydrogen bond) with the mineral and collagen phases by water are involved in toughening of bone tissues. Previous evidence has shown that the interaction of water with the mineral and collagen phases could inflict significant impacts on the mechanical behavior of bone. To this end, we propose in this exploratory proposal to study the contribution of polar interactions and hydrogen bonding ability of water to the mechanical behavior of bone using a novel experimental design and state-of-the-art techniques. Such understanding will help decipher the role of water in sustaining the toughness of bone and further facilitate the understanding of age-related changes in bone ultrastructure that obstruct the contribution of water to the tissue toughness. The hypothesis of this study is that water molecules affect the interaction between the mineral and collagen phases through both polar interactions and hydrogen bonding, thus imposing a significant effect on the toughness of bone. To test the hypothesis, two specific aims will be addressed: 1) to determine the effect of polar (van der Waals) forces and hydrogen bonding ability of water molecules on the interaction between the mineral and collagen phases; and 2) to determine the effect of polar (van der Waals) interactions and hydrogen bonding ability of water molecules on the mechanical behavior of bone. Combining the results obtained from Aim 1 and 2, the role of water in sustaining the toughness of bone will be elucidated. PUBLIC HEALTH RELEVANCE: Previous evidence has indicated that the role of water in sustaining the toughness of bone diminishes with increasing age. A systematic study using start-of-the-art techniques is proposed to elucidate the toughening mechanism of water to bone at ultrastructural levels. Such understanding will assist elucidate age-related changes in bone ultrastructure and its correlation with age-related bone fractures.