LEAP-HI: Design, Fabrication, and Multiscale Understanding of Biolubricants Using Synthetic Biology, Glycoengineering, and Biomimetic Synthesis

有效的润滑对于维持有效运转和减缓生命系统的退化至关重要。哺乳动物的关节用滑液润滑，口腔用唾液润滑，眼睛、呼吸道和胃肠道的上皮层覆盖有润滑的粘膜层。相反，不良的润滑性是关节炎或干眼等疾病的原因，也是全关节置换和隐形眼镜等医疗器械失效的根源。除了生物学之外，适当的润滑对发动机、发动机和车辆的功能也至关重要。摩擦增加占车辆燃料消耗的15%，并导致大型船舶运动阻力的60%-70%。因此，除了对生命系统的重要应用外，生物学还为润滑剂的设计提供了一个极好的模板，可以极大地降低各种人造系统的能源消耗。这一领先的美国繁荣、健康和基础设施工程(LEAP-HI)跨学科项目将设计、合成和测试新的润滑剂家族，以了解和治疗疾病，并作为润滑合成系统的模板。自然界中的一系列润滑行为是由粘蛋白介导的，粘蛋白是一种糖蛋白，通过蛋白质骨架与组织结合，并通过糖侧链将水吸引到表面，从而实现有效的润滑。例如，关节软骨表面的摩擦系数低至0.001，低于冰上的摩擦系数，并通过专门的粘蛋白润滑剂和透明质酸的相互作用进行润滑，形成微尺度的润滑层。该项目将研究使用润滑剂和透明质酸及其相互作用作为模板，以设计、制造和表征在多个长度尺度上润滑和保护生物系统的重组和合成润滑剂。其目标是：1)利用合成生物学、糖工程和仿生合成开发新一代生物润滑剂；2)在纳米、微观和宏观尺度上了解这些材料的润滑机理；3)评估新润滑剂治疗医疗条件的潜力。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。

Effective lubrication is critical to maintaining the efficient functioning and slowing the degradation of living systems. Mammalian joints are lubricated with synovial fluid, oral cavities are lubricated with saliva, and epithelial layers in the eye, respiratory airway, and gastrointestinal tract are coated with lubricating mucosal layers. Conversely, inferior lubrication is the cause of diseases such as arthritis or dry eye and is at the root of failure of medical devices such as total joint replacements and contact lenses. Beyond biology, proper lubrication is critical for the function of motors, engines, and vehicles. Increased friction accounts for up to 15% of fuel consumption in vehicles and results in 60-70 percent of resistance to motion of large ships. Thus, in addition to important applications to living systems, biology presents an excellent template for the design of lubricants that can greatly reduce energy consumption in a variety of man-made systems. This Leading Engineering for America's Prosperity, Health, and Infrastructure (LEAP-HI) interdisciplinary project will design, synthesize, and test new families of lubricants to understand and treat disease and to serve as templates for lubricating synthetic systems. An array of lubricating behaviors in nature are mediated by mucins, glycoproteins that achieve efficient lubrication by binding with tissues via a protein backbone and attracting water to surfaces via sugar side chains. For example, the articular cartilage surface has friction coefficients as low as 0.001, lower than ice-on-ice, and is lubricated by interactions of the specialized mucin lubricin and hyaluronic acid to form a microscale lubricating layer. The project will investigate the use lubricin and hyaluronic acid and their interactions as a template for designing, fabricating, and characterizing recombinant and synthetic lubricants that lubricate and protect biological systems at multiple length scales. The goal is to: 1) develop a new generation of biolubricants using synthetic biology, glycoengineering, and biomimetic synthesis; 2) understand mechanisms of lubrication of these materials at the nano-, micro-, and macroscales; and 3) evaluate the potential of the new lubricants to treat medical conditions.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.