What are the mechanisms by which cells establish and maintain collagen fibril-rich tissues?


  • Prof Karl Kadler

    University of Manchester

Project summary

Collagen is the most abundant structural protein in vertebrates. It occurs as centimetre-long fibrils in connective tissues such as skin, tendon, ligament, cartilage and blood vessels. A primary function of the fibrils is to 'stress shield' cells from the potentially damaging forces imposed on tissues by everyday activities like walking. A good analogy is the buildings in which we live and work – there are thousands of tons of concrete above our heads, but the walls protect us by a phenomenon called stress shielding. Collagen fibrils are made during early adulthood and last for our entire lives. This raises an important question about how cells protect the fibrils and if failure of a protective mechanism underlies chronic diseases such as tendinopathies, osteoarthritis and heart disease. Professor Kadler hypothesises that the circadian clock regulates the synthesis and removal of a mechano-protective matrix whose job it is to protect the precious collagen fibrils from being damaged by wear and tear. Using genetic manipulation, mechanical testing and by studying the protein secretory pathway in cells, Professor Kadler aims to understand the role of the circadian clock in tissue maintenance. The work could lead to new ways of preventing chronic diseases of tendons, ligaments, cartilage, skin and blood vessels.