Cell adhesion molecules have diverse roles in development, tissue organisation and tumour progression. But are distinct characteristics of the molecule important in each case? To address this question, Carl Figdor and colleagues have taken the unusual step of using atomic force microscopy (AFM) on living cells to investigate the kinetics and mechanics of the activated leukocyte cell adhesion molecule (ALCAM). ALCAM is involved in several dynamic situations–it engages in both homotypic interactions (important for maintaining tissue architecture and in metastasis) and heterotypic interactions with CD6 (important for association between dendritic cells and T cells). The authors measured the strength of adhesion between single ALCAM-expressing cells on the tip of the probe used in AFM and surfaces, coated with either ALCAM or CD6 molecules, under different degrees of external loading (see p. 3965). They find that, at physiologically relevant forces, the ALCAM-ALCAM interaction is much more labile than the ALCAM-CD6 interaction. This has not been apparent from soluble-ligand-binding assays and indicates that the interactions have very different underlying kinetic and mechanical features. The authors suggest that the different strengths of the homotypic and heterotypic associations reflect their distinct roles in migration of melanoma cells, binding between early dendritic cells and T cells, and dendritic-cell-induced T-cell proliferation.