The prion protein's (PrP) direct connection to fatal neurodegenerative diseases, collectively termed transmissible spongiform encephalopathies, has been the impetus for the intense research focus on this protein. PrP's precise physiological function has yet to be determined, although it has been identified as a metalloprotein capable of binding multiple copper ions and possibly zinc. Recent studies now indicate that prion self-recognition may be an important factor in the normal function and misfunction of this protein. We have developed fluorescently labeled models of the prion protein that allow prion-prion interactions and metal binding to be investigated on the molecular level. Peptides encompassing the full metal-binding region were anchored to the surface of small unilamellar vesicles and PrP-PrP interactions were monitored by fluorescence spectroscopy as a function of added metal. Both Cu²⁺ and Zn²⁺ were found to cause an increase in PrP-PrP interactions, whereas other metals such as Ni²⁺, Co²⁺ and Ca²⁺ had no effect. The binding of either of these cofactors appear to act as a switch that induces PrP-PrP interactions in a reversible manner. Overall, our results indicate that PrP may be a bifunctional molecule capable of responding to fluctuations in both neuronal Cu²⁺ and Zn²⁺ levels.