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致衰性疾病，仅在美国就有数百万人受到影响。软骨是一种有助于减少骨骼之间摩擦的垫子，当软骨受损时，就会导致关节炎等疾病，导致疼痛。该学院早期职业发展(CALEAR)奖旨在了解关节软骨表面如何引导和控制摩擦。除了覆盖在骨骼末端的软骨外，滑液也是关节的天然润滑剂，可以减少摩擦。软骨和滑液的结合可以保持关节的健康，这要归功于附着在软骨表面的润滑分子。本研究主要研究软骨表面润滑剂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、表面化学、生物学和摩擦学。该项目还支持一些教育和推广活动，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。润滑膜的形成在运动过程中至关重要，以润滑和保护关节表面。软骨细胞外基质表面的分子成分为润滑分子提供了锚定位置，从而为负载/能量耗散膜的组装提供了平台。胶原蛋白家族在调节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维连接蛋白及其各种构象在调节滑液成分吸附和耐磨性能方面的作用被忽视。该奖项通过确定软骨表面纤维连接蛋白在调节关节边界润滑和磨损保护中调节滑液成分的吸附和保留方面的作用，填补了这一知识空白。为了验证这一假设，这个项目将：i)开发关节软骨表面模型来控制分子组成和构象，ii)量化滑液成分的吸附，以及iii)进行纳米机械和纳米摩擦学表征，以建立纤维连接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，被认为值得支持。