Investigating the Mobile Fraction of Basement Membranes

Project Summary Basement membranes are strong thin sheets of extracellular matrix, and they are found throughout the human body: under epithelia, surrounding muscles and nerves and organs, and separating tissues. Their structure and function are critical for many aspects of human health, including mechanical support of tissues and muscles, embryonic morphogenesis, filtration of the blood in the kidney, blood-brain barrier function, resisting tumor metastasis, and wound healing. The most prevalent protein in basement membranes is collagen IV, which is crosslinked into a covalently-bound polymer network and gives the basement membrane its mechanical strength. Basement membranes and Collagen IV are highly conserved throughout the animal kingdom. Using Drosophila as a model, we recently found that there appear to be two fractions of collagen IV, a core fraction that appears stable and a mobile fraction that is more dynamic. In this R21 project, we will investigate the significance of these two fractions for the structure and function of basement membranes and begin to unravel the mechanisms governing their different stabilities.