Biomechanics Of Noncollagenous Osteocalcin/Osteopontin Protein Complex In Bone

骨骼是一种复合材料，由矿物质、胶原蛋白和非胶原蛋白组成，这些蛋白质在不同大小的结构中相互交织，从分子到整个骨骼。在最小的层次上，胶原蛋白分子聚集成原纤维。原纤维通过纤维间界面处的“天然胶”进一步结合形成胶原原纤维束。该界面主要由骨钙素（OCN）和骨桥蛋白（OPN）等其他蛋白质组成。虽然人们普遍认为骨骼的力学性能，如刚度和抗骨折性直接归因于其成分的力学性能，但对胶原纤维界面的全面了解并不存在。一种计算方法被计划用于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对骨生物力学领域和对骨质疏松症等骨医学问题的理解做出贡献。通过与研究相结合，教育推广计划将有助于培养生物力学方面的多元化劳动力，培养两名博士生，让本科生接触研究计划，并通过“纳米探索者”计划的暑期实习吸引高中生。本文认为OCN/OPN复合物的断裂变形行为和能量耗散主要是由以下四个关键因素造成的：1)胶原微纤维中非胶原蛋白基质与矿物质间钙介导的静电键；2) OPN中的隐藏长度；3) OCN和OPN潜在的翻译后修饰位点；4)接口复合体内OCN/OPN的并行配置。为了验证研究假设，将首先建立原子模拟方法来研究矿物质与具有不同程度翻译后修饰的非胶原蛋白（OCN和OPN）之间的相互作用。随后，将通过探索一系列空间结构、加载条件和破坏模式来研究纤维间界面的生物力学。如果上述假设通过本研究得到证实，那么新的骨模型将考虑到非胶原OCN/OPN蛋白复合物在骨中的重要作用，而不仅仅是基于现象学模型。这将反过来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.