Several models have been proposed to explain the cytotoxicity of A beta oligomers. The structural polymorphism of the oligomers can account for the various toxic effects observed. By combining the use of conformation-specific antibodies and single particle tracking techniques, we have investigated the mobility of individual A beta 1-42 oligomers on the plasma membrane of living cells. Distinct structural types of A beta 1-42 oligomers were labeled with two different conformation-specific antibodies. While both types of oligomers showed a heterogeneous dynamic behavior, their overall mobility was found to be significantly different. Conversely, we discovered that other amyloid oligomers sharing a similar conformation but composed of different peptides (amylin and prion Sup35NM) display dynamic behaviors comparable to those found for A beta 1-42 oligomers. This study provides evidence for a link between the quaternary structure and the membrane mobility of proteins, revealing that structurally analogous supramolecular assemblies diffuse similarly in cells.