Living things move. Lubrication in living organisms is critical to minimize wear, damage, and energy loss. Joints are lubricated with synovial fluid, oral cavities are lubricated with saliva, and epithelia of the eye, respiratory airway, and gastrointestinal tract are coated with mucosa. Diseases such as arthritis, dry eye, and inflammatory bowel disease are characterized by inferior lubrication. Failure of medical devices and materials is tied to poor lubrication, such as wear of total joint replacements or corneal abrasions from contact lenses. This multi-disciplinary proposal seeks 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) apply these lubricants to solve important problems in living systems. These studies will give new insight into the processes by which living systems move efficiently and yield novel lubricants used as therapies and as templates for synthetic systems.