Biomechanics Of Noncollagenous Osteocalcin/Osteopontin Protein Complex In Bone

骨中非胶原骨钙素/骨桥蛋白复合物的生物力学

• 批准号: 1727960
• 负责人: Dong Qian
• 金额: $ 35.97万
• 依托单位: University of Texas at Dallas
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1727960&HistoricalAwards=false
• 关键词: Biomechanics; Noncollagenous; Osteocalcin; Osteopontin; Protein

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.

骨是由矿物质、胶原蛋白和非胶原蛋白组成的复合材料，它们以不同大小的结构相互交织，从分子到整个骨。在最小的水平上，胶原蛋白分子组装成原纤维。原纤维通过“天然胶”在原纤维间界面处进一步结合以形成胶原原纤维束。该界面主要由其他蛋白质如骨钙素（OCN）和骨桥蛋白（OPN）构成。虽然人们普遍认为，骨的机械性能，如刚度和抗断裂性直接归因于其成分的机械性能，但对胶原纤维界面的全面理解并不存在。 一种计算方法计划研究的胶原纤维界面的蛋白质的生物力学。该项目的成功实施有望为骨生物力学领域和骨质疏松症等骨医学问题的理解做出贡献。通过与研究的整合，教育推广计划将有助于生物力学培训两名博士生的多元化劳动力的发展，使本科生接触研究计划，并通过暑期实习在“NanoExplorer”计划吸引高中生。据推测，断裂和变形行为以及OCN/OPN复合物的形成主要由四个关键因素决定：1）胶原微纤维中非胶原蛋白基质与矿物质之间的钙介导的静电键; 2）OPN的隐藏长度; 3）OCN和OPN中潜在的翻译后修饰位点; 4）OCN/OPN在界面复合物中的平行构型。为了验证这一研究假设，我们将首先建立一种原子模拟方法来研究矿物质与具有不同翻译后修饰程度的非胶原蛋白（OCN和OPN）之间的相互作用。随后，将通过探索一系列空间配置、载荷条件和失效模式来研究纤维间界面的生物力学。如果通过本研究证实了上述假设，则预计新的骨模型将考虑骨中非胶原OCN/OPN蛋白复合物的重要作用，而不是仅基于现象学模型的那些。这反过来又将对正在进行的骨和其他组织力学研究产生重大影响。

项目成果

Tensile and torsional elastomer fiber artificial muscle by entropic elasticity with thermo-piezoresistive sensing of strain and rotation by a single electric signal

• DOI: 10.1039/d0mh01003k
• 发表时间: 2020-12-01
• 期刊: MATERIALS HORIZONS
• 影响因子: 13.3
• 作者: Wang, Run;Shen, Yanan;Liu, Zunfeng
• 通讯作者: Liu, Zunfeng

Torsional refrigeration by twisted, coiled, and supercoiled fibers

通过扭曲、卷曲和超卷曲纤维进行扭转制冷

• DOI: 10.1126/science.aax6182
• 发表时间: 2019-10-11
• 期刊: SCIENCE
• 影响因子: 56.9
• 作者: Wang, Run;Fang, Shaoli;Baughman, Ray H.
• 通讯作者: Baughman, Ray H.

Deformation Mechanisms of “Two-Part” Natural Adhesive in Bone Interfibrillar Nano-Interfaces

骨纤维间纳米界面“双组分”天然粘合剂的变形机制

• DOI: 10.1021/acsbiomaterials.9b00588
• 发表时间: 2018
• 期刊: ACS Biomaterials Science & Engineering
• 影响因子: 5.8
• 作者: Morsali, Reza;Dai, Zhengwei;Wang, Yang;Qian, Dong;Minary-Jolandan, Majid
• 通讯作者: Minary-Jolandan, Majid

Ultrafast Pulsed Laser Induced Nanocrystal Transformation in Colloidal Plasmonic Vesicles

• DOI: 10.1002/adom.201800726
• 发表时间: 2018-09
• 期刊: Advanced Optical Materials
• 影响因子: 9
• 作者: M. Karim;Xiuying Li;P. Kang;J. Randrianalisoa;Dineli T. S. Ranathunga;S. Nielsen;Zhenpeng Qin;D. Qian

An efficient solution algorithm for space–time finite element method

• DOI: 10.1007/s00466-018-1603-8
• 发表时间: 2018-07
• 期刊: Computational Mechanics
• 影响因子: 4.1
• 作者: Rui Zhang;L. Wen;Jin-you Xiao;D. Qian