Further Studies on the Interaction of Migrating Keratinocytes with Fibrinogen

If glass implants placed under one edge of a skin wound in the adult newt are coated with fibrinogen (FGN), keratinocytes from the wound periphery migrate onto the implant. To learn more about the site(s) in FGN that permits this migration, we exposed keratinocytes to implants coated with forms of FGN containing modifications or deletions in the 3 most commonly studied cell binding sites; the RGDF sequence at Aa 95–98, RGDS at Aα 572–575 and the carboxy terminal 12 amino acids in the γA chain. Recombinant FGN with either RGD sequence altered to RGE supported migration as well as unmodified FGN did. Replacement of the carboxy terminal 4 amino acids in the γA chain by a 20 amino acid sequence that disrupts the ability of the γ terminus to mediate platelet aggregation (the γ' variant) likewise had no effect. Nor did simultaneous antibody blockade of the RGDS, RGDF, and γA sites have any effect. At its best, Dhem1, a fragment containing the RGDS and γA sites, produced only about half as much migration as the ...