(A) A micrometer-sized silica sphere is covered with a lipid bilayer (red) equipped with synaptobrevin (syb) and brought into contact with a solid-supported bilayer (green) on silica functionalized with the ∆N-complex. The following discrete states are distinguished: (1) free probe, docking in contact (2), followed by hemifusion (3) and, eventually, full merging of the two bilayers (4). Desorption from the surface (5) reveals a large adhesion energy due to strong attractive van der Waals interactions between the two silica surfaces. (B) Experimental force cycle in which the aforementioned intermediates are assigned. (Inset) Fluorescence images of the colloidal probe after successful fusion events at the end of an experiment. Left: red channel, center: green channel, right: merging of the two channels. (Scale bar, 10 µm.)