Biomechanics Of Noncollagenous Osteocalcin/Osteopontin Protein Complex In Bone

骨是一种复合材料，由矿物质、胶原蛋白和非胶原蛋白组成，它们交织在从分子到整个骨骼的不同大小的结构中。在最小的水平上，胶原分子组装成纤维。纤维进一步通过纤维间界面处的天然胶粘剂粘合在一起形成胶原纤维束。这种界面主要由其他蛋白质组成，如骨钙素(OCN)和骨桥蛋白(OPN)。虽然人们普遍认为骨骼的力学性质，如硬度和抗折性，直接归因于其成分的力学性质，但对胶原纤维界面的全面了解还不存在。计划用一种计算方法来研究胶原纤维界面蛋白质的生物力学。该项目的成功实施有望为骨生物力学领域和了解骨质疏松等骨医学问题做出贡献。通过与研究的结合，一个教育推广计划将有助于培养一支多样化的生物力学劳动力队伍，培训两名博士生，让本科生接触研究计划，并通过暑期实习吸引高中生参加纳米探索者计划。假设OCN/OPN复合体中的断裂和变形行为以及相关的能量耗散主要由四个关键因素造成：1)非胶原蛋白基质与胶原微原纤维中的矿物之间的钙介导的静电键；2)OPN中的隐藏长度；3)OCN和OPN中潜在的翻译后修饰位点；4)OCN/OPN在界面复合体中的平行配置。为了验证研究假设，首先将建立一个原子模拟方法来研究具有不同翻译后修饰程度的矿物质与非胶原蛋白(OCN和OPN)之间的相互作用。随后，将通过探索一系列的空间构型、载荷条件和破坏模式来研究纤维间界面的生物力学。如果上述假说通过这项研究得到证实，预计新的骨模型将考虑非胶原性OCN/OPN蛋白复合体在骨中的重要作用，而不仅仅是基于现象学模型。这反过来将对正在进行的骨和其他组织的力学研究产生重大影响。

Bone is a composite material that is made of minerals, collagen and noncollagenous proteins that are intertwined in structures of different sizes ranging from the molecular to the whole bone. At the smallest level, collagen molecules assemble into fibrils. The fibrils are further bonded to form collagen fibril bundles by a 'natural glue' at the interfibrillar interface. This interface is primarily made of other proteins such osteocalcin (OCN) and osteopontin (OPN). While it is generally recognized that the mechanical properties of the bone such as stiffness and fracture resistance are directly attributed to the mechanical properties of its constituents, a comprehensive understanding for the collagen fibrillar interface does not exist. A computational approach is planned to study the biomechanics of the proteins of the collagen fibril interface. Successful implementation of this project is expected to contribute to the field of bone biomechanics and understanding medical issues with bone such as osteoporosis. Through integration with research, an educational outreach program will contribute to the development of a diverse workforce in biomechanics training two PhD students, exposing undergraduate students to the research program, and engaging high school students through summer internship in the "NanoExplorer" program.It is hypothesized that the fracture and deformation behavior and the associated energy dissipation in the OCN/OPN complex are mainly contributed by four key factors: 1) Calcium-mediated electrostatic bonds between noncollagenous protein matrix and mineral in collagen microfibril; 2) Hidden length in OPN; 3) Potential post-translational modification sites in OCN and OPN; 4) Parallel configuration of OCN/OPN within the interface complex. To test the research hypothesis, an atomistic simulation approach will be first established to study the interaction between minerals and non-collagenous proteins (OCN and OPN) with different degrees of post-translational modifications. Subsequently, the biomechanics of interfibrillar interfaces will be investigated by exploring a range of spatial configurations, loading conditions and failure modes. If the above hypothesis is confirmed through this research, it is expected that new models of bone will take into account the important effects of noncollagenous OCN/OPN protein complex in bone rather than those based on merely phenomenological models. This will in turn significantly impact the ongoing research on the mechanics of bone and other tissues.