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Investigation of structural interactions of Fibronectin type III domains

Final Activity Report Summary - FNIII-STRUCTURES (Investigation of structural interactions of Fibronectin type III domains)

Our work focussed on human fibronectin, a major component of the matrix that holds cells together in tissues. Fibronectin is important for an array of processes, including embryo development, wound healing and also cancer metastasis. We proposed to study how fibronectin molecules come together, in a process known as fibrillogenesis, to form this matrix. Important unanswered questions in the field were related to how the matrix creation was regulated, how fibronectin transmitted signals to cells and how it interacted with other components of this matrix.

We studied these questions over a two year period. We found that the conformation of fibronectin, i.e. the way this molecule looked like in space, played an important role in controlling the various activities. We showed that altering specific aspects of this conformation, for example transiting between a compact and an extended fibronectin state, led to the initial steps of matrix creation as well as to signals for cells to migrate. Cell mobility also depended on the consistency and properties of the matrix surrounding them, e.g. on how dense the matrix was and whether cells could cleave their way through. We showed conclusively that fibronectin interacted with specific sites on collagen, which was a biomolecule comprising over 25 % of the body protein content by weight. Collagen was also an important matrix component; hence this interaction with fibronectin had clear implications on the matrix structure. We continued working on better identifying this interaction in order to shed light on how cells migrated.