(582ec) Engineering a Proteolytically Stable and Biologically Active Fibronectin

Fibronectin is an essential an essential component of the extracellular matrix. It is proteolytically degraded in cellular responses such as migration and proliferation. However, excessive proteolysis of fibronectin is associated with tumor invasion and chronic wound healing. A study is presented on stabilizing fibronectin by conjugating it to polyethylene glycol through lysine residues. Proteolytic stability of the conjugates was determined by adding protease and quantifying the number and amount of proteolytic fragments with time. The activity of fibronectin conjugated to polyethylene glycol was measured by its ability to engage in intermolecular interactions with cells, fibronectin fragments and other extracellular matrix components. This study demonstrates that conjugating polyethylene glycol to fibronectin stabilizes it against proteolytic degradation. The study also shows that proteolytic stability and activity of the fibronectin conjugates is dependent on the length of polyethylene glycol and the extent of polyethylene glycol conjugation. The study provides new insight into potential mechanisms of bioengineering fibronectin for therapeutic uses.