CAREER: Mechanobiology of Load-bearing Interfaces

职业：承载界面的力学生物学

• 批准号: 2239665
• 负责人: Roberto Andresen Eguiluz
• 金额: $ 52.33万
• 依托单位: University of California - Merced
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2239665&HistoricalAwards=false
• 关键词: CAREER; Mechanobiology; Load; bearing; Interfaces

Arthritis is a significant debilitating disease that affects millions of people in the US alone. When the cartilage, a cushion that helps reduce friction between bones, gets damaged, it leads to diseases such as arthritis, causing pain. This Faculty Early Career Development (CAREER) award aims to understand how the surface of articular cartilage direct and control friction. In addition to the cartilage covering the ends of bones, synovial fluid also serves as the natural lubricant of joints that reduces friction. Combined cartilage and synovial fluid maintain healthy joints, thanks to the lubricating molecules that stick to the surface of the cartilage. This study focuses on examining the biomechanical behaviors of lubricating molecules sticking to the cartilages. Results from this research will help identify molecular strategies to treat arthritis. This research is highly interdisciplinary involving biophysics, polymer physics, surface chemistry, biology, and tribology. This project also supports several educational and outreach activities involving the inclusion and training of underrepresented groups in biomaterials and mechanobiology-relevant research.Lubricant film formation is critical during locomotion to lubricate and wear-protect the surface of articulated joints. The molecular components of the cartilage extracellular matrix surface provide anchoring sites for lubricating molecules, thus serving as a platform for the assembly of the load/energy-dissipative films. The role of the collagens family in mediating the adsorption of lubricating and wear-protecting molecules has been studied in depth. However, the role of fibronectin, another important cartilage extracellular matrix component, and its various conformations in regulating synovial fluid component adsorption and wear-protecting properties has been overlooked. This award fills this knowledge gap by determining the role of cartilage surface fibronectin in mediating the adsorption and retention of synovial fluid components to regulate joint boundary lubrication and wear protection. To test this hypothesis, this project will: i) develop articular cartilage surface models to control molecular compositions and conformations, ii) quantify synovial fluid component adsorption, and iii) perform nanomechanical and nanotribological characterizations to establish relationships between fibronectin-mediated synovial fluid film formation and tribological performance.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

关节炎是一种严重的使人衰弱的疾病，仅在美国就影响了数百万人。当软骨（有助于减少骨骼之间摩擦的缓冲垫）受损时，会导致关节炎等疾病，引起疼痛。该学院早期职业发展（CAREER）奖旨在了解关节软骨表面如何引导和控制摩擦。除了覆盖骨头末端的软骨外，滑液还可以充当关节的天然润滑剂，减少摩擦。由于粘附在软骨表面的润滑分子，软骨和滑液的结合可以维持健康的关节。这项研究的重点是检查粘附在软骨上的润滑分子的生物力学行为。这项研究的结果将有助于确定治疗关节炎的分子策略。这项研究是高度跨学科的，涉及生物物理学、聚合物物理学、表面化学、生物学和摩擦学。该项目还支持多项教育和外展活动，涉及生物材料和机械生物学相关研究中代表性不足的群体的纳入和培训。润滑油膜的形成在运动过程中对于润滑和磨损保护关节表面至关重要。软骨细胞外基质表面的分子成分为润滑分子提供锚定位点，从而充当负载/能量耗散膜组装的平台。胶原蛋白家族在介导润滑和磨损保护分子的吸附中的作用已被深入研究。然而，另一种重要的软骨细胞外基质成分纤连蛋白及其多种构象在调节滑液成分吸附和磨损保护性能中的作用却被忽视了。该奖项通过确定软骨表面纤连蛋白在介导滑液成分的吸附和保留以调节关节边界润滑和磨损保护方面的作用，填补了这一知识空白。为了检验这一假设，该项目将：i) 开发关节软骨表面模型来控制分子组成和构象，ii) 量化滑液成分吸附，以及 iii) 进行纳米力学和纳米摩擦学表征，以建立纤连蛋白介导的滑液膜形成和摩擦学性能之间的关系。该奖项反映了 NSF 的法定使命，并被认为是值得的 通过使用基金会的智力优势和更广泛的影响审查标准进行评估来提供支持。